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1.
Adv Exp Med Biol ; 1255: 29-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949388

RESUMO

T cells recognize peptides bound to major histocompatibility complex (MHC) class I and class II molecules at the cell surface. This recognition is accomplished by the expression of T cell receptors (TCR) which are required to be diverse and adaptable in order to accommodate the various and vast number of antigens presented on the MHCs. Thus, determining TCR repertoires of effector T cells is necessary to understand the immunological process in responding to cancer progression, infection, and autoimmune development. Furthermore, understanding the TCR repertoires will provide a solid framework to predict and test the antigen which is more critical in autoimmunity. However, it has been a technical challenge to sequence the TCRs and provide a conceptual context in correlation to the vast number of TCR repertoires in the immunological system. The exploding field of single-cell sequencing has changed how the repertoires are being investigated and analyzed. In this review, we focus on the biology of TCRs, TCR signaling and its implication in autoimmunity. We discuss important methods in bulk sequencing of many cells. Lastly, we explore the most pertinent platforms in single-cell sequencing and its application in autoimmunity.


Assuntos
Receptores de Antígenos de Linfócitos T/genética , Análise de Sequência , Análise de Célula Única , Animais , Autoimunidade/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
2.
Mol Immunol ; 124: 218-228, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32615275

RESUMO

Autoreactive T cells may contribute to post-viral myocarditis induced with Coxsackievirus B3 (CVB3), but the underlying mechanisms of their generation are unclear. Here, we have comprehensively analyzed the generation of antigen-specific, autoreactive T cells in the mouse model of CVB3 infection for antigens implicated in patients with myocarditis/dilated cardiomyopathy. First, comparative analysis of CVB3 proteome with five autoantigens led us to identify three mimicry epitopes, one each from adenine nucleotide translocator 1 (ANT), sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and cardiac troponin I. None of these induced cross-reactive T cell responses. Next, we generated major histocompatibility complex (MHC) class II dextramers to enumerate the frequencies of antigen-specific T cells to determine whether T cells with multiple antigen specificities are generated by CVB3 infection. These analyses revealed appearance of CD4 T cells positive for SERCA2a 971-990, and cardiac myosin heavy chain-α (Myhc) 334-352 dextramers, both in the periphery and also in the hearts of CVB3-infected animals. While ANT 21-40 dextramer+ T cells were inconsistently detected, the ß1-adrenergic receptor 181-200/211-230 or branched chain α-ketoacid dehydrogenase kinase 111-130 dextramer+ cells were absent. Interestingly, SERCA2a 971-990, Myhc 334-352 and ANT 21-40 dextramer+ cells were also detected in the liver indicating that they may have a pathogenic role. Finally, we demonstrate that the SERCA2a 971-990-reactive T cells generated in CVB3 infection could transfer disease to naïve mice. The data suggest that CVB3 infection can lead to the generation of autoreactive T cells for multiple antigens indicating a possibility that the autoreactive T cells localized in the liver can potentially circulate and contribute to the development of viral myocarditis.


Assuntos
Autoantígenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Infecções por Coxsackievirus/imunologia , Miocardite/imunologia , Miocardite/virologia , Animais , Autoimunidade/imunologia , Reações Cruzadas , Modelos Animais de Doenças , Enterovirus Humano B , Feminino , Masculino , Camundongos
4.
Scand J Immunol ; 92(4): e12945, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32697368

RESUMO

In the past decades, clinical and experimental evidence has demonstrated that psoriasis is an immune-mediated inflammatory disease of the skin that occurs in genetically susceptible individuals. Psoriasis also shows clear autoimmune pathomechanisms, but specific cellular targets for the onset and maintenance of psoriatic lesions were not established until 2014. Since then, four psoriasis autoantigens were discovered, namely cathelicidin LL-37, melanocytic ADAMTSL5, lipid antigen PLA2G4D and keratin 17. Autoreactive T cells against these autoantigens were found in a number of patients with moderate-to-severe plaque psoriasis. Moreover, the discovery of autoantibodies against LL-37 and ADAMTSL5 and their strong association with psoriatic arthritis (PsA) suggest a potential role of these autoantibodies in the pathogenesis of PsA. This review discusses the current studies on psoriatic autoantigens and the associated circulating autoantibodies and their mechanisms involved in the development and maintenance of psoriatic plaques. Recent autoimmune evidence fuelled the discussion on psoriasis as an autoimmune skin disorder and has the potential to develop new treatment strategies with protective and therapeutic antigen-targeted methods.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Psoríase/imunologia , Proteínas ADAMTS/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/imunologia , Autoimunidade/imunologia , Fosfolipases A2 do Grupo IV/imunologia , Humanos , Queratina-17/imunologia
5.
Scand J Immunol ; 92(4): e12943, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32697399

RESUMO

Type 1 diabetes is an autoimmune disease typically starting in childhood that culminates in the destruction of insulin-producing beta cells in the pancreas. Although type 1 diabetes is considered to be a primarily T cell-mediated disease, B cells clearly participate in the autoimmune process, as autoantibodies recognizing pancreatic islet antigen commonly appear in circulation before the onset of the disease. T cells providing helper functions to B cells have recently been shown to be involved in the pathogenesis of a wide range of antibody-associated immune disorders. These T cells include CXCR5-positive follicular T helper (Tfh) cells, and a recently described closely related CXCR5-negative subset coined peripheral T helper (Tph) cells. Here, we review the current state of knowledge on different B cell helper T cell subsets, focusing on their potential involvement in the development of type 1 diabetes.


Assuntos
Linfócitos B/imunologia , Diabetes Mellitus Tipo 1/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Autoimunidade/imunologia , Humanos
6.
Neurology ; 95(9): 399-401, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32651290
7.
Nature ; 582(7812): 416-420, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499641

RESUMO

Regulatory T (Treg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity1. Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties2, can promote autoimmunity and/or facilitate more effective tumour immunity3,4. A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective Treg therapies for autoimmune disease and cancer. The availability of new functional genetic tools has enabled the possibility of systematic dissection of the gene regulatory programs that modulate Foxp3 expression. Here we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse Treg cells and applied this technology to perform a targeted loss-of-function screen of around 500 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We identified several modulators of Foxp3 expression, including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin-modifying complex, was revealed to be a positive regulator that stabilized Foxp3 expression; whereas the screen suggested that Rnf20, an E3 ubiquitin ligase, can serve as a negative regulator of Foxp3. Treg-specific ablation of Usp22 in mice reduced Foxp3 protein levels and caused defects in their suppressive function that led to spontaneous autoimmunity but protected against tumour growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient Treg cells could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in Treg cells. These results reveal previously unknown modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for Treg immunotherapies for cancer and autoimmune disease.


Assuntos
Sistemas CRISPR-Cas , Fatores de Transcrição Forkhead/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Autoimunidade/imunologia , Células Cultivadas , Fatores de Transcrição Forkhead/biossíntese , Edição de Genes , Regulação da Expressão Gênica , Humanos , Imunoterapia , Masculino , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/prevenção & controle , Estabilidade Proteica , Reprodutibilidade dos Testes , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Ubiquitina Tiolesterase/deficiência , Ubiquitina Tiolesterase/metabolismo , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/metabolismo
8.
Nat Immunol ; 21(8): 950-961, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32572241

RESUMO

A contribution of epigenetic modifications to B cell tolerance has been proposed but not directly tested. Here we report that deficiency of ten-eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. Mechanistically, in the absence of Tet2 and Tet3, downregulation of CD86, which normally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take place. The importance of dysregulated CD86 expression in Tet2- and Tet3-deficient B cells was further demonstrated by the restriction, albeit not complete, on aberrant T and B cell activation following anti-CD86 blockade. Tet2- and Tet3-deficient B cells had decreased accumulation of histone deacetylase 1 (HDAC1) and HDAC2 at the Cd86 locus. Thus, our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity.


Assuntos
Autoimunidade/imunologia , Linfócitos B/imunologia , Antígeno B7-2/imunologia , Proteínas de Ligação a DNA/imunologia , Dioxigenases/imunologia , Proteínas Proto-Oncogênicas/imunologia , Animais , Doenças Autoimunes/imunologia , Epigênese Genética/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
9.
Nature ; 582(7810): 89-94, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32483373

RESUMO

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.


Assuntos
Proteína C9orf72/genética , Microbioma Gastrointestinal/fisiologia , Gliose/microbiologia , Gliose/patologia , Inflamação/genética , Inflamação/microbiologia , Medula Espinal/patologia , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , Animais , Antibacterianos/farmacologia , Autoimunidade/efeitos dos fármacos , Autoimunidade/genética , Autoimunidade/imunologia , Movimento Celular/efeitos dos fármacos , Citocinas/imunologia , Transplante de Microbiota Fecal , Feminino , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Gliose/genética , Gliose/prevenção & controle , Inflamação/patologia , Inflamação/prevenção & controle , Mutação com Perda de Função/genética , Masculino , Camundongos , Microglia/imunologia , Microglia/microbiologia , Microglia/patologia , Medula Espinal/imunologia , Medula Espinal/microbiologia , Taxa de Sobrevida
11.
Int Arch Allergy Immunol ; 181(6): 476-480, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248193

RESUMO

BACKGROUND: CD8+ regulatory T cells (CD8+ Tregs) are relatively recently described T cell subsets that have been shown to regulate various T cell responses and appear to play a role in autoimmunity. However, their effects on B cells have not been explored. OBJECTIVES: In this investigation we examine the effect of CD8+ Tregs on various subsets of peripheral B cells include naïve B cells, transitional B cells, marginal zone B cells, IgM memory B cells, class switched memory B cells, and plasmablasts, and on the expression of B cell-activating factor receptor (BAFF-R). METHODS: CD8+ T cells were first purified and then activated with anti-CD3/CD28 beads to generate CD8+ Tregs. Purified CD19+ B cells were cultured alone or with sorted CD8+ Tregs (CD8+CD183+CCR7+CD45RA-) and activated with anti-CD40 monoclonal antibody and CpG. B cell subsets and the expression of BAFF-R on naïve and memory B cells were analyzed using various monoclonal antibodies and corresponding control isotypes. Ten thousand cells were acquired and analyzed by FACSCalibur using the FlowJo software. RESULTS: CD8+ Tregs selectively and significantly suppressed plasmablasts without any significant effect on other B cell subsets or on the expression of BAFF-R. CONCLUSION: CD8+ Tregs may play a role in autoimmunity by regulating antibody production via suppression of plasmablasts.


Assuntos
Autoimunidade/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T Reguladores/imunologia , Células Cultivadas , Humanos
14.
Arch Endocrinol Metab ; 64(1): 66-70, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32187261

RESUMO

Objective Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder that is frequently seen in the eastern Mediterranean region. The thyroid gland can be affected in FMF patients through autoimmunity or amyloidosis. Here, we aimed to evaluate the structure and functions of the thyroid gland in addition to possible autoimmunity in FMF patients. Subjects and methods The study was conducted by the Endocrinology and Metabolism and Internal Medicine Departments. Thirty FMF patients and 30 age and gender-matched healthy controls were enrolled in the study. Free thyroxin (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone (TSH), and anti-thyroid peroxidase (anti-TPO) autoantibodies were investigated. Detailed thyroid grayscale and Doppler Ultrasonography examinations and shear-wave elastosonography (SWE) were performed in the patient and control groups. Results Anti-TPO was detected in 24% (n = 7) of the patients. On the grayscale US, mean thyroid volumes were similar between the FMF and the control groups (p > 0.05). By Doppler US, thyroid vascularity observed was detected in 10.3% (n = 3) of the patients. SWE revealed that the mean velocity value of right vs. left lobe in the patient group was 1.77 ± 0.45 m/s and 1.95 ± 0.51 m/s, respectively. Compared to the control group, the mean velocity values were significantly higher in the right (p = 0.004) and left (p = 0.01) lobes of the patient group. The mean stiffness value in the patient group was also significantly higher in the right and left lobes [10.13 ± 5.65 kPa (p = 0.005) and 12.24 ± 6.17 kPa (p = 0.02), respectively]. Conclusion Recognizing the complications of FMF early in the course of the disease is as important as the early diagnosis of the disorder. Based on this, thyroid functions and changes in its structure should be evaluated carefully for early diagnosis of a possible coexisting thyroid disorder. Arch Endocrinol Metab. 2020;64(1):66-70.


Assuntos
Autoanticorpos/imunologia , Autoimunidade/imunologia , Febre Familiar do Mediterrâneo/imunologia , Febre Familiar do Mediterrâneo/fisiopatologia , Glândula Tireoide/imunologia , Adulto , Autoanticorpos/sangue , Estudos de Casos e Controles , Febre Familiar do Mediterrâneo/diagnóstico por imagem , Feminino , Humanos , Iodeto Peroxidase/sangue , Iodeto Peroxidase/imunologia , Masculino , Tireotropina/sangue , Tireotropina/imunologia , Tri-Iodotironina/sangue , Tri-Iodotironina/imunologia , Ultrassonografia Doppler
15.
Am J Kidney Dis ; 76(2): 265-281, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32220510

RESUMO

Systemic lupus erythematosus is a multisystem autoimmune disease that commonly affects the kidneys. Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus and a major risk factor for morbidity and mortality. The pathophysiology of LN is heterogeneous. Genetic and environmental factors likely contribute to this heterogeneity. Despite improved understanding of the pathogenesis of LN, treatment advances have been few and risk for kidney failure remains unacceptably high. This installment in the Core Curriculum of Nephrology provides an up-to-date review of the current understanding of LN epidemiology, pathogenesis, diagnosis, and treatment. Challenging issues such as the management of LN in pregnancy, timing of transplantation, and the evolving role of corticosteroid use in the management of LN are discussed. We review the currently accepted approach to care for patients with LN and highlight deficiencies that need to be addressed to better preserve long-term kidney health and improve outcomes in LN.


Assuntos
Corticosteroides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/terapia , Transplante de Rim , Nefrite Lúpica , Diálise Renal , Imunidade Adaptativa/imunologia , Distribuição por Idade , Autoanticorpos/imunologia , Autoimunidade/imunologia , Biópsia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunidade Inata/imunologia , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Falência Renal Crônica/etiologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Quimioterapia de Manutenção , Masculino , Ácido Micofenólico/uso terapêutico , Gravidez , Complicações na Gravidez , Urinálise
16.
J Leukoc Biol ; 107(5): 739-748, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32202348

RESUMO

Obesity-induced insulin resistance is one of the largest noncommunicable disease epidemics that we are facing at the moment. Changes in lifestyle and greater availability of low nutritional value, high caloric food has led to the highest rates of obesity in history. Obesity impacts the immune system and obesity-associated inflammation contributes to metabolic diseases, such as type 2 diabetes. Both the adaptive and the innate immune system play a role in the regulation of glycemic control, and there is a need to understand how metabolic imbalances drive disease pathogenesis. This review discusses the cell types, mediators, and pathways that contribute to immunologic-metabolic crosstalk and explores how the immune system might be targeted as a strategy to treat metabolic disease.


Assuntos
Autoimunidade/imunologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Inflamação/fisiopatologia , Obesidade/complicações , Obesidade/imunologia , Obesidade/metabolismo
17.
J Immunol ; 204(7): 1736-1745, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32111731

RESUMO

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.


Assuntos
Autoimunidade/imunologia , Linfócitos B/imunologia , Interleucina-1/imunologia , Miastenia Gravis/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th17/imunologia , Adulto , Autoanticorpos/imunologia , Células Cultivadas , Feminino , Humanos , Imunidade Humoral/imunologia , Masculino , Pessoa de Meia-Idade
18.
J Immunol ; 204(7): 1787-1797, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32111734

RESUMO

Ag-specific tolerizing immunotherapy is considered the optimal strategy to control type 1 diabetes, a childhood disease involving autoimmunity toward multiple islet antigenic peptides. To understand whether tolerizing immunotherapy with a single peptide could control diabetes driven by multiple Ags, we coencapsulated the high-affinity CD4+ mimotope (BDC2.5mim) of islet autoantigen chromogranin A (ChgA) with or without calcitriol (1α,25-dihydroxyvitamin D3) into liposomes. After liposome administration, we followed the endogenous ChgA-specific immune response with specific tetramers. Liposome administration s.c., but not i.v., induced ChgA-specific Foxp3+ and Foxp3- PD1+ CD73+ ICOS+ IL-10+ peripheral regulatory T cells in prediabetic mice, and liposome administration at the onset of hyperglycemia significantly delayed diabetes progression. After BDC2.5mim/calcitriol liposome administration, adoptive transfer of CD4+ T cells suppressed the development of diabetes in NOD severe combined immunodeficiency mice receiving diabetogenic splenocytes. After BDC2.5mim/calcitriol liposome treatment and expansion of ChgA-specific peripheral regulatory T cells. IFN-γ production and expansion of islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8+ T cells were also suppressed in pancreatic draining lymph node, demonstrating bystander tolerance at the site of Ag presentation. Thus, liposomes encapsulating the single CD4+ peptide, BDC2.5mim, and calcitriol induce ChgA-specific CD4+ T cells that regulate CD4+ and CD8+ self-antigen specificities and autoimmune diabetes in NOD mice.


Assuntos
Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/imunologia , Ilhotas Pancreáticas/imunologia , Lipossomos/imunologia , Linfócitos T Reguladores/imunologia , Animais , Doenças Autoimunes/terapia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Diabetes Mellitus Tipo 1/terapia , Feminino , Tolerância Imunológica/imunologia , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Peptídeos/imunologia
19.
Immunity ; 52(2): 342-356.e6, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32023490

RESUMO

Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting γδ T (γδT17) cells and Th17 cells. However, T cells from Il17a-/- mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1ß, and IL-23. Furthermore, treatment with IL-1ß or IL-17A at induction of EAE restores disease in Il17a-/- mice. Importantly, mobilization of IL-1ß-producing neutrophils and inflammatory monocytes and activation of γδT17 cells is reduced in Il17a-/- mice. Our findings demonstrate that a key function of IL-17A in central nervous system (CNS) autoimmunity is to recruit IL-1ß-secreting myeloid cells that prime pathogenic γδT17 and Th17 cells.


Assuntos
Autoimunidade/imunologia , Interleucina-17/imunologia , Interleucina-1beta/metabolismo , Linfócitos Intraepiteliais/imunologia , Células Mieloides/imunologia , Células Th17/imunologia , Animais , Autoantígenos/imunologia , Autoimunidade/genética , Sistema Nervoso Central/imunologia , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Interleucina-17/antagonistas & inibidores , Interleucina-17/deficiência , Interleucina-17/metabolismo , Interleucina-1beta/imunologia , Interleucina-23/imunologia , Interleucina-23/metabolismo , Linfócitos Intraepiteliais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Monócitos/metabolismo , Células Mieloides/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Células Th17/metabolismo
20.
Allergol. immunopatol ; 48(1): 18-25, ene.-feb. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-186587

RESUMO

Introduction and objectives: Connective tissue diseases are inflammatory, autoimmune diseases and threaten quality of life. To determine the relationship between staining patterns of antinuclear antibodies and antibodies against extractable nuclear antigens in patients with connective tissue disease. Materials and methods: Observational, basic, analytical and transversal study. Study conducted in the Immunology Service of the Arzobispo Loayza National Hospital between January 2017 and June 2017. We analyzed 291 samples of patients with CTD and for the detection of anti-nuclear antibody staining patterns, the immunological kit and observation with microscope of at 40X Immunofluorescence and for the detection of the antibodies against extractable nuclear antigens. The Immunoblot method was employed. Statistical analyses were carried out with the statistical package SPSS version 21 for Windows. We used the Pearson Chi-square test for the categorical variables, a value of p < 0.05 was considered significant. Results: There was a significant relationship p < 0.05 of the homogeneous pattern, the mottled pattern with Anti-histones (p = 0.000), Anti-nucleosomes (p = 0.000), Anti-Ro 52 (p = 0.000), Anti-SSA (p = 0.001), Anti-SSB (p = 0.003), Anti-dsDNA (p = 0.000) with the Pearson Chi-square test. There was a significant relationship of p < 0.05 of the centromeric pattern with Anti-Cenp B (p = 0.000) with Fisher's exact statistic. Conclusions: There was a significant relationship between the anti-nuclear antibody staining patterns and the antibodies to the core extractable antigens in patients with systemic lupus erythematosus, Sjögren's syndrome, Calcinosis, Raynaud's phenomenon, esophageal Dysmotility, sclerodactyly and Telangiectasia (CREST), Scleroderma and Polymyositis


No disponible


Assuntos
Humanos , Anticorpos Antinucleares/análise , Anticorpos/análise , Antígenos Nucleares/imunologia , Doenças do Tecido Conjuntivo/imunologia , Autoimunidade/imunologia , DNA/análise , Doenças do Tecido Conjuntivo/diagnóstico , Estudos Transversais , Microscopia de Fluorescência , Técnica Indireta de Fluorescência para Anticorpo , Proteína Centromérica A , Autoanticorpos/imunologia
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