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1.
Nat Commun ; 11(1): 4504, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908131

RESUMO

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury.


Assuntos
Microambiente Celular/imunologia , Sistemas de Liberação de Medicamentos/instrumentação , Fator de Crescimento Neural/administração & dosagem , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/terapia , Tecidos Suporte , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Preparações de Ação Retardada/administração & dosagem , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/administração & dosagem , Lipossomos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Neural/farmacocinética , Regeneração Nervosa/imunologia , Ratos , Recuperação de Função Fisiológica/imunologia , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Traumatismos da Medula Espinal/imunologia
2.
Scand J Immunol ; 92(5): e12956, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32767795

RESUMO

In a healthy person, metabolically quiescent T lymphocytes (T cells) circulate between lymph nodes and peripheral tissues in search of antigens. Upon infection, some T cells will encounter cognate antigens followed by proliferation and clonal expansion in a context-dependent manner, to become effector T cells. These events are accompanied by changes in cellular metabolism, known as metabolic reprogramming. The magnitude and variation of metabolic reprogramming are, in addition to antigens, dependent on factors such as nutrients and oxygen to ensure host survival during various diseases. Herein, we describe how metabolic programmes define T cell subset identity and effector functions. In addition, we will discuss how metabolic programs can be modulated and affect T cell activity in health and disease using cancer and autoimmunity as examples.


Assuntos
Autoimunidade/imunologia , Metabolismo Energético/imunologia , Ativação Linfocitária/imunologia , Neoplasias/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Microambiente Celular/imunologia , Humanos , Modelos Imunológicos , Neoplasias/metabolismo , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/metabolismo
3.
J Leukoc Biol ; 108(1): 189-198, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645257

RESUMO

Acupuncture is a centuried and unfading treatment of traditional Chinese medicine, which has been proved to exert curative effects on various disorders. Numerous works have been put in to uncover the effective mechanisms of acupuncture. And the interdependent interaction between acupuncture and acupoint microenvironment is a crucial topic. As a benign minimally invasive stimulation, the insertion and manipulation of needle at acupoint could cause deformation of local connective tissue and secretion of various molecules, such as high mobility group box 1 and ATP. The molecules are secreted into extracellular space and bind to the corresponding receptors thus active NF-κB, MAPK, ERK pathways on mast cells, fibroblasts, keratinocytes, and monocytes/macrophages, among others. This is supposed to trigger following transcription and translation of immune factors and neural active substance, as well as promote the free ion movement (such as Ca2+ influx) and the expansion of blood vessels to recruit more immune cells to acupoint. Finally, acupuncture could enhance network connectivity of local microenvironment at acupoints. The earlier mentioned substances further act on a variety of receptors in local nerve endings, transmitting electrical and biochemical signals to the CNS, and giving full play to the acupuncture action. In conclusion, we portrayed a neuro-immune microenvironment network of acupoints that medicates the acupuncture action, and would lay a foundation for the systematic study of the complex network relationship of acupoints in the future.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Microambiente Celular/imunologia , Sistema Nervoso/imunologia , Humanos
4.
Nat Commun ; 11(1): 3677, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699279

RESUMO

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.


Assuntos
Linfócitos B/imunologia , Microambiente Celular/imunologia , Quimiocina CXCL13/metabolismo , Células Dendríticas Foliculares/imunologia , Imunidade Adaptativa , Animais , Linfócitos B/citologia , Linfócitos B/metabolismo , Catepsina B/genética , Catepsina B/metabolismo , Linhagem Celular , Quimiocina CXCL13/imunologia , Simulação por Computador , Células Dendríticas Foliculares/citologia , Células Dendríticas Foliculares/metabolismo , Matriz Extracelular/metabolismo , Humanos , Camundongos , Camundongos Knockout , Microscopia de Fluorescência , Modelos Biológicos , Tonsila Palatina/citologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Células Estromais/imunologia , Células Estromais/metabolismo
5.
Scand J Immunol ; 92(3): e12920, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594535

RESUMO

The maintenance of inner integrity of an organism is founded on the proper performance of two immunity branches, innate and adaptive immune responses. Recently, it became apparent that subset of splenic B cells named marginal zone B cells (MZB cells) exhibits unique developmental and functional features that bridge these two immunity branches. Strategically positioned at the site where blood and lymph are filtered, MZB cells represent a population of sentinels that rapidly proliferate and differentiate into IgM plasmablast cells when encountered with blood-borne, thymus-independent (TI) Ags. Moreover, MZB cells have intrinsic capability to induce potent CD4+ helper T cell response and cytokine production upon stimulation with soluble antigens. Due to their ability to overcome a time gap prior the establishment of the full adaptive response towards pathogens, MZB cells connect and direct innate and adaptive immunity. An additional interesting characteristic of MZB cells is capacity to function as regulatory cells in autoimmune processes. MZB cells may also contribute to the control of autoimmunity via the induction of tolerance by apoptotic cells. Importantly, in the clear association with inflammation and autoimmunity, MZB cells may transform into MALT lymphoma, representing a concurrence point for the infection, immunity and malignancy. This paper presents an insight into the complex biology of marginal zone B cells and their role in intertwining and directing innate and adaptive immune processes at the physiological and pathological level.


Assuntos
Linfócitos B/imunologia , Linfócitos B/metabolismo , Suscetibilidade a Doenças , Homeostase , Baço/imunologia , Baço/metabolismo , Imunidade Adaptativa , Animais , Microambiente Celular/imunologia , Humanos , Ativação Linfocitária/imunologia , Baço/patologia
6.
Nat Immunol ; 21(6): 660-670, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32341509

RESUMO

Within germinal centers (GCs), complex and highly orchestrated molecular programs must balance proliferation, somatic hypermutation and selection to both provide effective humoral immunity and to protect against genomic instability and neoplastic transformation. In contrast to this complexity, GC B cells are canonically divided into two principal populations, dark zone (DZ) and light zone (LZ) cells. We now demonstrate that, following selection in the LZ, B cells migrated to specialized sites within the canonical DZ that contained tingible body macrophages and were sites of ongoing cell division. Proliferating DZ (DZp) cells then transited into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. Multidimensional analysis revealed distinct molecular programs in each population commensurate with observed compartmentalization of noncompatible functions. These data provide a new three-cell population model that both orders critical GC functions and reveals essential molecular programs of humoral adaptive immunity.


Assuntos
Microambiente Celular/genética , Microambiente Celular/imunologia , Centro Germinativo/citologia , Centro Germinativo/fisiologia , Animais , Biomarcadores , Biologia Computacional/métodos , Imunofluorescência , Perfilação da Expressão Gênica , Genômica/métodos , Camundongos , Fosforilação , Proteoma , Proteômica/métodos , Transcriptoma
7.
Mol Immunol ; 120: 122-129, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114182

RESUMO

Dendritic cells (DCs) orchestrate adaptive immune responses. In healthy individuals, DCs are drivers and fine-tuners of T cell responses directed against invading pathogens or cancer cells. In parallel, DCs control autoreactive T cells, thereby maintaining T cell tolerance. Under various disease conditions, a disruption of this delicate balance can lead to chronic infections, tumor evasion, or autoimmunity. While great efforts have been made to unravel the origin and development of this powerful cell type in mice, only little is known about the ontogeny of human DCs. Here, we summarize the current understanding of the developmental path of DCs from hematopoietic stem cells to fully functional DCs in their local tissue environment and provide a template for the identification of DCs across various tissues.


Assuntos
Células Dendríticas/citologia , Células Dendríticas/imunologia , Animais , Autoimunidade , Diferenciação Celular/imunologia , Microambiente Celular/imunologia , Células Dendríticas/classificação , Células-Tronco Hematopoéticas/classificação , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Tolerância Imunológica , Camundongos , Modelos Imunológicos , Especificidade de Órgãos , Fenótipo
8.
Immunity ; 52(3): 434-451, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32187515

RESUMO

Self-maintaining resident macrophages populate all mammalian organs. In addition to their role as immune sentinels, macrophages also perform day-to-day functions essential to tissue homeostasis. The homeostatic functions of macrophages are regulated by so-called tissular "niches" that control the size of the macrophage population and imprint tissue-specific identity. Here, we review the mechanisms underlying self-maintenance of distinct macrophage populations and outline the organizing principles of the macrophage niche. We examine recent studies that uncovered mutually beneficial cell-cell circuits established between macrophages and their niche and propose a modular view of tissues that integrates the resident macrophage as an essential component of each individual module. Manipulating macrophage niche cells to control the function of resident macrophages in vivo might have therapeutic value in various disease settings.


Assuntos
Microambiente Celular/imunologia , Homeostase/imunologia , Macrófagos/imunologia , Especificidade de Órgãos/imunologia , Animais , Sobrevivência Celular/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucinas/imunologia , Interleucinas/metabolismo , Fator Estimulador de Colônias de Macrófagos/imunologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo
9.
Nat Immunol ; 21(3): 309-320, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31953534

RESUMO

Tissue-resident memory T cells (TRM cells) are critical for cellular immunity to respiratory pathogens and reside in both the airways and the interstitium. In the present study, we found that the airway environment drove transcriptional and epigenetic changes that specifically regulated the cytolytic functions of airway TRM cells and promoted apoptosis due to amino acid starvation and activation of the integrated stress response. Comparison of airway TRM cells and splenic effector-memory T cells transferred into the airways indicated that the environment was necessary to activate these pathways, but did not induce TRM cell lineage reprogramming. Importantly, activation of the integrated stress response was reversed in airway TRM cells placed in a nutrient-rich environment. Our data defined the genetic programs of distinct lung TRM cell populations and show that local environmental cues altered airway TRM cells to limit cytolytic function and promote cell death, which ultimately leads to fewer TRM cells in the lung.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Reprogramação Celular/genética , Reprogramação Celular/imunologia , Epigênese Genética/imunologia , Memória Imunológica/genética , Pulmão/imunologia , Animais , Apoptose/imunologia , Linfócitos T CD8-Positivos/citologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Microambiente Celular/genética , Microambiente Celular/imunologia , Feminino , Pulmão/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia
10.
J Cell Physiol ; 235(1): 281-293, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31215024

RESUMO

The inflammatory microenvironment in the joints is one of the critical issues during osteoarthritis (OA) and also the main factor that may aggravate symptoms. Under inflammatory microenvironment, M1 macrophages are activated and produce large numbers of proinflammatory mediators, leading to the production of degradative enzymes, the disturbance of chondrocyte apoptosis and cartilage catabolic processes, and finally the deterioration of OA. In the present study, we reveal that the overexpression of osteopontin (OPN), a cytokine, and a matrix protein involved in arthritis and chondrocyte apoptosis in OA, could exacerbate the inflammatory microenvironment in OA via promoting the production of proinflammation cytokines and the levels of degradative enzymes in M1 macrophages, therefore, enhancing the cytotoxicity of M1 macrophage on chondrocytes. XIST expression significantly increases in OA tissue specimens. XIST serves as a competing endogenous RNA for miR-376c-5p to compete with OPN for miR-376c-5p binding, thus counteracting miR-376c-5p-mediated OPN suppression. XIST knockdown could improve the inflammatory microenvironment in OA via acting on M1 macrophages, subsequently affecting the apoptosis of cocultured chondrocytes. miR-376c-5p inhibition exerts an opposing effect on M1 macrophages and cocultured chondrocytes, as well as significantly reverses the effect of XIST knockdown. As a further confirmation, XIST and OPN mRNA expression significantly increased in OA tissues and was positively correlated in tissue samples. In summary, we provide a novel mechanism of macrophages and the inflammatory microenvironment affecting chondrocyte apoptosis. XIST and OPN might be potential targets for OA treatment, which needs further in vivo experimental confirmation.


Assuntos
Condrócitos/imunologia , Macrófagos/imunologia , MicroRNAs/genética , Osteoartrite/imunologia , Osteopontina/metabolismo , RNA Longo não Codificante/genética , Apoptose/imunologia , Células Cultivadas , Microambiente Celular/imunologia , Técnicas de Cocultura , Citocinas/biossíntese , Humanos , Macrófagos/citologia , Osteopontina/genética
12.
Genome Med ; 11(1): 73, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771646

RESUMO

BACKGROUND: Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized. METHODS: In this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples. RESULTS: We inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, ß, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival. CONCLUSIONS: Our comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies.


Assuntos
Suscetibilidade a Doenças , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Adulto , Fatores Etários , Linfócitos B/imunologia , Linfócitos B/metabolismo , Microambiente Celular/genética , Microambiente Celular/imunologia , Criança , Regiões Determinantes de Complementaridade , Humanos , Leucemia Mieloide Aguda/patologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Sequência de RNA , Linfócitos T/imunologia , Linfócitos T/metabolismo
13.
Autoimmunity ; 52(7-8): 242-250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31661985

RESUMO

Salivary and lacrimal gland involvement is a characteristic feature of primary Sjögren's syndrome (pSS), where tissue destruction is mediated by mononuclear cell infiltration, resulting in lacrimal and salivary gland impairment. We have previously shown distinct prevalence of adipose tissue replacement in the minor salivary gland tissue from pSS patients. The salivary gland microenvironment was further examined through microarray analysis, identifying signalling pathways that promoted adipose tissue development, inflammation, and lymphoma. As B cells may also contribute to disease progression, we now aimed to study the B cell pattern with regard to adipocyte development in pSS. Double immunohistochemical staining of paraffin-embedded salivary gland tissue from 22 pSS patients and 11 non-SS tissue controls was employed, using the characteristic pSS autoantigens Ro52 or Ro60, alongside CD27. Additional CD138/CD20 double staining was also performed to identify the plasma- and general B- cell pattern. Our results demonstrated CD27-positive Ro52 and Ro60 specific cells observed within and in close proximity to the adipose tissue. CD138-positive plasma cells were also seen in areas of adipose tissue replacement, while the CD20+ cells were located within focal infiltrates, forming distinct B cell zones. The quantification of CD138+ and CD20+ cells revealed elevated numbers of CD138+ cells in areas of fatty infiltration, and also interstitially, in the salivary glands of pSS patients when compared to non-SS controls. A significant increase (p < .01) in CD138+ cells close to areas of fatty infiltration, and interstitially, with increasing fatty infiltration and focus score was further observed in pSS patients. A correlation between the number of CD20+ B cell zones/mm2 of salivary gland tissue and focus score values was also witnessed in the patients (r2 = 0.6047, p < .001). In conclusion, autoantigen-specific B cells and plasma cells appear prominent in areas of fatty infiltration in salivary glands of pSS patients, where an increase in CD138+ plasma cells and CD20+ B cells, in relation to both fatty and focal infiltration, suggests their active involvement in promoting inflammation. Further studies are needed to assess whether these adipocytes are also a result of tissue repair.


Assuntos
Adipócitos/patologia , Autoantígenos/genética , Linfócitos B/patologia , Glândulas Salivares/patologia , Síndrome de Sjogren/patologia , Adipócitos/imunologia , Adulto , Idoso , Antígenos CD20/genética , Antígenos CD20/imunologia , Autoantígenos/imunologia , Autoimunidade , Linfócitos B/imunologia , Estudos de Casos e Controles , Movimento Celular , Microambiente Celular/genética , Microambiente Celular/imunologia , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Saliva/química , Saliva/imunologia , Glândulas Salivares/imunologia , Transdução de Sinais , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Sindecana-1/genética , Sindecana-1/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia
14.
Adv Exp Med Biol ; 1186: 99-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654387

RESUMO

There is an increasing effort toward generating replacement cells for neuronal application due to the nonregenerative nature of these tissues. While much progress has been made toward developing methodologies to generate these cells, there have been limited improvements in functional restoration. Some of these are linked to the degenerative and often nonreceptive microenvironment that the new cells need to integrate into. In this chapter, we will focus on the status and role of the immune microenvironment of the retina during homeostasis and disease states. We will review changes in both innate and adaptive immunity as well as the role of immune rejection in stem cell replacement therapies. The chapter will end with a discussion of immune-modulatory strategies that have helped to ameliorate these effects and could potentially improve functional outcome for cell replacement therapies for the eye.


Assuntos
Retina , Transplante de Células-Tronco , Imunidade Adaptativa , Microambiente Celular/imunologia , Humanos , Imunidade Inata , Imunomodulação , Neurônios/fisiologia , Retina/imunologia , Degeneração Retiniana/imunologia , Degeneração Retiniana/patologia , Degeneração Retiniana/terapia
15.
J Immunol Res ; 2019: 2164017, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565659

RESUMO

Inflammation is a well-known feature of heart failure. Studies have shown that while some inflammation is required for repair during injury and is protective, prolonged inflammation leads to myocardial remodeling and apoptosis of cardiac myocytes. Various types of immune cells are implicated in myocardial inflammation and include neutrophils, macrophages, eosinophils, mast cells, natural killer cells, T cells, and B cells. Recent clinical trials have targeted inflammatory cascades as therapy for heart failure with limited success. A better understanding of the temporal course of the infiltration of the different immune cells and their contribution to the inflammatory process may improve the success for therapy. This brief review outlines the major cell types involved in heart failure, and some of their actions are summarized in the supplementary figure.


Assuntos
Microambiente Celular , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Miocárdio/imunologia , Miocárdio/metabolismo , Animais , Microambiente Celular/genética , Microambiente Celular/imunologia , Suscetibilidade a Doenças , Insuficiência Cardíaca/diagnóstico , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Miocárdio/patologia , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo
16.
Adv Immunol ; 143: 75-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607368

RESUMO

Mononuclear phagocytes, including monocytes and macrophages, are a central component of the host's innate immune system designated to protect against invading pathogens. However, these cells do not only interact with various parts of the innate and adaptive immune system, but also fulfill indispensable duties during the control of tissue homeostasis and organ function. Moreover, macrophages are crucially involved in tissue remodeling and repair in response to damage. Simultaneously, mononuclear phagocytes might also contribute to the pathogenesis of various inflammatory and autoimmune diseases. In particular, their potential role in inflammatory joint diseases such as rheumatoid arthritis (RA) has drawn increasing attention and substantially shaped our general understanding of the role of monocytes and macrophages during health and disease. This review summarizes our current knowledge about the origin and function of mononuclear phagocytes within the joint and addresses their involvement in joint inflammation.


Assuntos
Artrite Reumatoide/imunologia , Cápsula Articular/citologia , Macrófagos/imunologia , Monócitos/imunologia , Líquido Sinovial/citologia , Animais , Doenças Autoimunes/metabolismo , Microambiente Celular/imunologia , Citocinas/metabolismo , Humanos , Imunidade Inata , Cápsula Articular/imunologia , Macrófagos/citologia , Macrófagos/metabolismo , Monócitos/citologia , Monócitos/metabolismo , Líquido Sinovial/imunologia
17.
Front Immunol ; 10: 2284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616442

RESUMO

Autoimmune diseases are a physiological state wherein immune responses are directed against and damage the body's own tissues. Cytokines secreted by infiltrated inflammatory cells contribute to the pathogenesis of autoimmune diseases. TIPE2, one of the four family members of Tumor necrosis factor-α induced protein-8 (TNFAIP8), is a negative regulator of innate and adaptive immunity and plays essential roles in the maintenance of immune tolerance. However, studies on the role of TIPE2 during the development of autoimmune diseases have generated contradictory results. In the current study, we sought to determine the role of TIPE2 during the development of IMQ-induced psoriasis and Experimental Autoimmune Uveitis (EAU) in mice. Our study revealed that, while TIPE2-deficiency alleviates psoriasis, it exacerbates the development of EAU. Further studies demonstrated that, although TIPE2-deficient T cells produced more IL-17A, they do not migrate efficiently to the local inflammatory site, i.e., the skin. This in turn led to the decreased IL-17A production in the skin and consequently reduced the severity of psoriasis in TIPE2-deficient mice. However, although TIPE2-deficient T cells still produced more IL-17A in EAU model, they migrate into the inflamed eye as efficient as TIPE2-sufficient T cells, and consequently exacerbates the development of EAU in TIPE2-deficient mice. Taken together, these results indicate that TIPE2 may either promote or suppress autoimmunity depending on the specific inflammatory microenvironment in different types of autoimmune diseases.


Assuntos
Doenças Autoimunes/imunologia , Movimento Celular/imunologia , Microambiente Celular/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Linfócitos T/imunologia , Uveíte/imunologia , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Movimento Celular/genética , Microambiente Celular/genética , Modelos Animais de Doenças , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Interleucina-17/genética , Interleucina-17/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Camundongos , Camundongos Knockout , Linfócitos T/patologia , Uveíte/genética , Uveíte/patologia
18.
Mol Cell ; 76(2): 232-242, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31586546

RESUMO

Why do cells have so many ways to die? Why does "cellular suicide" exist at all? In the war against pathogens and rogue cells, organisms developed cellular suicide as a last resort. Fighting an evolutionary arms race, cell death pathways have adapted and multiplied to cover the complexity of the foes the immune system faces. In this review, we discuss the different types of cell death, the underlying signaling events, and their unequal ability to trigger an immune response. We also comment on how to use our knowledge of cell death signaling to improve the efficacy of cancer treatment. We argue that cell death is integral to the immune response and acts as a beacon, a second messenger, that guides both immune system and tissue micro-environment to ensure tissue repair and homeostasis. Memento mori-"remember you must die"-as failure to do so opens the way to chronic infection and cancer.


Assuntos
Apoptose/imunologia , Microambiente Celular/imunologia , Neoplasias/imunologia , Transdução de Sinais/imunologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Ferroptose/imunologia , Humanos , Imunoterapia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Necroptose/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Terapia Viral Oncolítica , Piroptose/imunologia , Transdução de Sinais/efeitos dos fármacos , Evasão Tumoral
19.
Mol Biol Rep ; 46(5): 4675-4684, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31529342

RESUMO

The purpose of this study was to test the hypothesis that different cytokine profiles may exist in the follicular fluid of endometriosis (EM) patients undergoing in vitro fertilization (IVF), as these differences may provide insights into the pathogenesis of the disease. This was a cross-sectional study conducted at the reproductive center of a medical university hospital. The study included 49 patients receiving IVF. 20 infertile women with proven EM and 29 women without diagnosed EM (control group) were evaluated. Follicular fluid (FF) and serum were collected at the time of follicle aspiration and the concentrations of 38 cytokines were determined by multiplexed immunoassay. The results indicated that the levels of IL-4, IL-13, IL-3 and IL-1α were significantly increased in the FF of women with EM, while levels of IFN-γ, IL-17A, MDC and MIP-1α were decreased compared with in the control subjects. In conclusions, the immune microenvironment of the FF in patients with EM is altered. This may contribute to the pathologic mechanism responsible for the poor outcome of IVF in patients with EM.


Assuntos
Microambiente Celular/imunologia , Endometriose/diagnóstico , Endometriose/etiologia , Folículo Ovariano/imunologia , Biomarcadores , Citocinas/biossíntese , Citocinas/sangue , Endometriose/metabolismo , Feminino , Fertilização In Vitro/efeitos adversos , Líquido Folicular/imunologia , Líquido Folicular/metabolismo , Hormônios/sangue , Hormônios/metabolismo , Humanos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia
20.
Immunol Rev ; 292(1): 9-23, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31538349

RESUMO

Lymph nodes (LNs) are at the cross roads of immunity and tolerance. These tissues are compartmentalized into specialized niche areas by lymph node stromal cells (LN SCs). LN SCs shape the LN microenvironment and guide immunological cells into different zones through establishment of a CCL19 and CCL21 gradient. Following local immunological cues, LN SCs modulate activity to support immune cell priming, activation, and fate. This review will present our current understanding of LN SC subsets roles in regulating T cell tolerance. Three major types of LN SC subsets, namely fibroblastic reticular cells, lymphatic endothelial cells, and blood endothelial cells, are discussed. These subsets serve as scaffolds to support and regulate T cell homeostasis. They contribute to tolerance by presenting peripheral tissue antigens to both CD4 and CD8 T cells. The role of LN SCs in regulating T cell migration and tolerance induction is discussed. Looking forward, recent advances in bioengineered materials and approaches to leverage LN SCs to induce T cell tolerance are highlighted, as are current clinical practices that allow for manipulation of the LN microenvironment to induce tolerance. Increased understanding of LN architecture, how different LN SCs integrate immunological cues and shape immune responses, and approaches to induce T cell tolerance will help further combat autoimmune diseases and graft rejection.


Assuntos
Microambiente Celular/imunologia , Tolerância Imunológica/imunologia , Linfonodos/imunologia , Células Estromais/imunologia , Linfócitos T/imunologia , Imunidade Adaptativa/imunologia , Animais , Quimiocina CCL19/imunologia , Quimiocina CCL19/metabolismo , Quimiocina CCL21/imunologia , Quimiocina CCL21/metabolismo , Humanos , Linfonodos/metabolismo , Células Estromais/metabolismo , Linfócitos T/metabolismo
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