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1.
Scand J Immunol ; 91(3): e12854, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31785109

RESUMO

Prion diseases are fatal neurodegenerative processes caused by the accumulation of the pathological prion protein, PrPSc . While pathological lesions are limited to the central nervous system (CNS), disease-specific proteins accumulate and replicate in secondary lymphoid organs prior to neuroinvasion, and their replication there depends on the abundance of cellular prion protein (PrPC ). PrPC is expressed in both central and peripheral lymphoid tissues, and up- or downregulates innate and adaptive immune responses. In addition to prion diseases, PrPC is also immunologically involved in other neurological disorders and infectious diseases, including Alzheimer's disease and human immunodeficiency virus infection. Herein, we summarize the expression and functions of PrPC in various immunocytes, as well as its immunological and pathological roles in neurodegeneration and infection.


Assuntos
Regulação da Expressão Gênica , Sistema Imunitário , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Animais , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade Inata , Proteínas PrPC/genética , Proteínas PrPC/metabolismo
2.
Biochim Biophys Acta Rev Cancer ; 1873(1): 188335, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816350

RESUMO

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor (TF) that is a member of the Per-Arnt-Sim family of proteins. AhR regulates diverse processes, including malignant transformation, hematopoietic cell development, and fate determination of immune cell lineages. Moreover, AhR forms a crucial link between innate and adaptive arms of the immune system. Malignant cells frequently evolve multiple mechanisms for suppressing tumor-specific responses, including the induction of suppressive pathways involving AhR and its metabolic byproducts in the tumor microenvironment that promote immune evasion and tumor progression. Thus, interest is high in further defining the role of AhR in carcinogenesis and immune development and regulation, particularly regarding the therapeutic interventions that unleash immune responses to cancer cells. Here, we provide an overview of the role of AhR in the regulation of innate and adaptive immune response and discuss the implications of targeting this pathway to augment the immune response in cancer patients.


Assuntos
Regulação da Expressão Gênica/genética , Sistema Imunitário/metabolismo , Neoplasias/genética , Receptores de Hidrocarboneto Arílico/genética , Microambiente Tumoral/genética , Imunidade Adaptativa/genética , Imunidade Adaptativa/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Imunidade Inata/genética , Imunidade Inata/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Receptores de Hidrocarboneto Arílico/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Microambiente Tumoral/imunologia
3.
Rev Chilena Infectol ; 36(3): 341-352, 2019 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-31859753

RESUMO

Pregnancy-associated malaria is an understudied event in Latin America. Most works about malaria in pregnancy have been conducted in Africa. These studies indicate that the infection generates immune response modulation and alterations in the placental environment, key factors for the proper development of the fetus and neonate. Immunity against Plasmodium spp is complex since involves several factors that increase the possible infection outcomes. One of these immunological outcomes is the immune response modulation towards a regulatory profile, which is advantageous for the persistence of the parasite in the host; additionally, it could generate adverse events in the general immune response of infected individuals. The objective of this review is to address the Plasmodium spp mechanisms of modulation in the host immune response and expose the consequences of malarial infections in the mother-neonate context.


Assuntos
Imunomodulação/fisiologia , Malária/imunologia , Plasmodium/imunologia , Complicações Parasitárias na Gravidez/imunologia , Feminino , Interações Hospedeiro-Parasita/imunologia , Humanos , Sistema Imunitário/imunologia , Recém-Nascido , Placenta/imunologia , Placenta/parasitologia , Plasmodium/fisiologia , Gravidez
4.
Semin Oncol ; 46(4-5): 385-392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31739997

RESUMO

There is no doubt that immunotherapy lies in the spotlight of current cancer research and clinical trials. However, there are still limitations in the treatment response in certain types of tumors largely due to the presence of the complex network of immunomodulatory and immunosuppressive pathways. These limitations are not likely to be overcome by current immunotherapeutic options, which often target isolated steps in immune pathways preferentially involved in adaptive immunity. Recently, we have developed an innovative anti-cancer immunotherapeutic strategy that initially elicits a strong innate immune response with subsequent activation of adaptive immunity in mouse models. Robust primary innate immune response against tumor cells is induced by toll-like receptor ligands and anti-CD40 agonistic antibodies combined with the phagocytosis-stimulating ligand mannan, anchored to a tumor cell membrane by biocompatible anchor for membrane. This immunotherapeutic approach results in a dramatic therapeutic response in large established murine subcutaneous tumors including melanoma, sarcoma, pancreatic adenocarcinoma, and pheochromocytoma. Additionally, eradication of metastases and/or long-lasting resistance to subsequent re-challenge with tumor cells was also accomplished. Current and future advantages of this immunotherapeutic approach and its possible combinations with other available therapies are discussed in this review.


Assuntos
Imunoterapia , Neoplasias/terapia , Imunidade Adaptativa , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Terapia Combinada , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade Inata , Imunomodulação , Imunoterapia/métodos , Ligantes , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptores Toll-Like/metabolismo , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
5.
Mol Biol (Mosk) ; 53(5): 815-829, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31661480

RESUMO

The modern era of research in immunology is characterized by an unprecedented level of detail about structural characteristics of the immune system and the regulation of activities of its numerous components, which function together as a whole distributed-parameter system. Mathematical modeling provides an analytical tool to describe, analyze, and predict the dynamics of immune responses by applying a reductionist approach. In modern systems immunology and mathematical immunology as a new interdisciplinary field, a great challenge is to formulate the mathematical models of the human immune system that reflect the level achieved in understanding its structure and describe the processes that sustain its function. To this end, a systematic development of multiscale mathematical models has to be advanced. An appropriate methodology should consider (1) the intracellular processes of immune cell fate regulation, (2) the population dynamics of immune cells in various organs, and (3) systemic immunophysiological processes in the whole host organism. Main studies aimed at modeling the intracellular regulatory networks are reviewed in the context of multiscale mathematical modelling. The processes considered determine the regulation of the immune cell fate, including activation, division, differentiation, apoptosis, and migration. Because of the complexity and high dimensionality of the regulatory networks, identifying the parsimonious descriptions of signaling pathways and regulatory loops is a pressing problem of modern mathematical immunology.


Assuntos
Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Modelos Imunológicos , Apoptose , Diferenciação Celular , Movimento Celular , Humanos , Transdução de Sinais
6.
Life Sci ; 238: 116923, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610191

RESUMO

Idiopathic membranous nephropathy (IMN) has recently attracted much attention due to the development of auto antibodies, anti-phospholipase A2 receptor and anti-thrombospondin type I domain-containing 7A on podocytes, the establishment of immune networks complexes in circulation as well as the development of autoreactive immune cells against kidney, in both innate and adaptive participants. The auto inflammatory responses in IMN leads to the dysfunction of glomerular cells to represent pathological status. T cells, as a crucial factor in the immune network, support B cell-related responses and develop inflammation and cytotoxicity. They have the most determining roles in the autoimmune diseases. Activation of T cells occurs just before their infiltration in kidney. This process is definitely accompanied by costimulatory factors and cytokines, in order to develop and increase the number of these cells. In addition, altered B cell signaling network by the B cell receptor and co receptors such as B cell-activating factor receptor (BAFFR) stimulates the autoimmune-related pathogenesis. Autoantigens exposure and kidney infiltration of naive T cells lead to their local development. Furthermore, losing peripheral immune tolerance towards kidney antigens, will result in IMN. The growing findings about different immune system factors, cells and molecular mechanism have also revealed new pathways of pathogenesis and diagnosis approaches, such as personalized medicine in MN patients. This review aims to discuss the recent findings in adaptive immune cells, and distinguishes between intact and undone researches about pathogenesis and molecular signaling pathways of immune system in MN disease.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Sistema Imunitário/imunologia , Animais , Humanos
7.
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
8.
Cytogenet Genome Res ; 159(2): 55-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31630146

RESUMO

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients.


Assuntos
Síndrome de Klinefelter/genética , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Genótipo , Humanos , Sistema Imunitário/imunologia , Infertilidade Masculina/genética , Infertilidade Masculina/imunologia , Síndrome de Klinefelter/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/fisiologia , Masculino , Fenótipo , Análise de Célula Única/métodos , Transcriptoma/genética , Transcriptoma/imunologia
9.
Rev Cardiovasc Med ; 20(3): 153-160, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601089

RESUMO

Exosomes, nanosized lipid bilayer membranous vesicles, are secreted by a variety of cells and contain protein, lipids, mRNA, miRNA, and signaling molecules that participate in intercellular material transfer and information exchange through binding, fusion or endocytosis. Exosomes mediate the gene expression of target cells and regulate pathological and physiological processes, thereby playing a key role in the occurrence and development of various diseases. Accumulated studies has shown that exosomes hold therapeutic potential though their anti-apoptotic and anti-fibrotic roles. They also have been shown to promote angiogenesis, inhibit ventricular remodeling and improve cardiac function, as well as inhibiting local inflammation and regulating the immune response. As such, exosomes represent a new target for the treatment of cardiovascular diseases. This review summarizes the literature in this field to date, including the basic biological characteristics of exosomes, and new progress in the understanding of the mechanisms of their involvement in immune regulation in cardiovascular diseases. In this way, it servrs as a basis for future research and the development of therapeutic exosomes.


Assuntos
Doenças Cardiovasculares/imunologia , Sistema Cardiovascular/imunologia , Exossomos/imunologia , Sistema Imunitário/imunologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Exossomos/metabolismo , Exossomos/transplante , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Prognóstico , Transdução de Sinais
10.
Int J Mol Sci ; 20(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533245

RESUMO

Extracellular heat shock proteins (ex-HSPs) have been found in exosomes, oncosomes, membrane surfaces, as well as free HSP in cancer and various pathological conditions, also known as alarmins. Such ex-HSPs include HSP90 (α, ß, Gp96, Trap1), HSP70, and large and small HSPs. Production of HSPs is coordinately induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), while matrix metalloproteinase 3 (MMP-3) and heterochromatin protein 1 are novel inducers of HSPs. Oncosomes released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP) by which immune evasion can be established. The concepts of RASP are: (i) releases of ex-HSP and HSP-rich oncosomes are essential in RASP, by which molecular co-transfer of HSPs with oncogenic factors to recipient cells can promote cancer progression and resistance against stresses such as hypoxia, radiation, drugs, and immune systems; (ii) RASP of tumor cells can eject anticancer drugs, targeted therapeutics, and immune checkpoint inhibitors with oncosomes; (iii) cytotoxic lipids can be also released from tumor cells as RASP. ex-HSP and membrane-surface HSP (mHSP) play immunostimulatory roles recognized by CD91+ scavenger receptor expressed by endothelial cells-1 (SREC-1)+ Toll-like receptors (TLRs)+ antigen-presenting cells, leading to antigen cross-presentation and T cell cross-priming, as well as by CD94+ natural killer cells, leading to tumor cytolysis. On the other hand, ex-HSP/CD91 signaling in cancer cells promotes cancer progression. HSPs in body fluids are potential biomarkers detectable by liquid biopsies in cancers and tissue-damaged diseases. HSP-based vaccines, inhibitors, and RNAi therapeutics are also reviewed.


Assuntos
Espaço Extracelular/metabolismo , Proteínas de Choque Térmico/metabolismo , Evasão da Resposta Imune , Vigilância Imunológica , Animais , Biomarcadores , Vesículas Extracelulares/metabolismo , Proteínas de Choque Térmico/antagonistas & inibidores , Proteínas de Choque Térmico/genética , Humanos , Evasão da Resposta Imune/genética , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Vigilância Imunológica/genética , Imunomodulação , Biópsia Líquida , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Receptores de Superfície Celular/metabolismo
11.
Int J Mol Sci ; 20(19)2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31546715

RESUMO

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.


Assuntos
Anticoncepcionais Orais/metabolismo , Hormônios/metabolismo , Imunomodulação , Fígado/imunologia , Fígado/metabolismo , Fitoestrógenos/metabolismo , Anticoncepcionais Orais/farmacologia , Feminino , Hormônios/farmacologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunomodulação/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estrutura Molecular , Fitoestrógenos/farmacologia , Fatores Sexuais
12.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489895

RESUMO

Inflammation is a physiological process by which the body responds to external insults and stress conditions, and it is characterized by the production of pro-inflammatory mediators such as cytokines. The acute inflammatory response is solved by removing the threat. Conversely, a chronic inflammatory state is established due to a prolonged inflammatory response and may lead to tissue damage. Based on the evidence of a reciprocal regulation between inflammation process and calcium unbalance, here we described the involvement of a calcium sensor in cardiac diseases with inflammatory drift. Indeed, the Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated in several diseases with an inflammatory component, such as myocardial infarction, ischemia/reperfusion injury, pressure overload/hypertrophy, and arrhythmic syndromes, in which it actively regulates pro-inflammatory signaling, among which includes nuclear factor kappa-B (NF-κB), thus contributing to pathological cardiac remodeling. Thus, CaMKII may represent a key target to modulate the severity of the inflammatory-driven degeneration.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiopatias/metabolismo , Miocardite/metabolismo , Miocárdio/metabolismo , Animais , Biomarcadores , Cálcio/metabolismo , Suscetibilidade a Doenças , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/patologia , Miocardite/diagnóstico , Miocardite/etiologia , Miocárdio/patologia , Estresse Oxidativo , Transdução de Sinais
13.
Magy Onkol ; 63(3): 202-207, 2019 Sep 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533140

RESUMO

In recent years widespread use of immuno-oncology drugs are in the focus of modern systemic anticancer therapies. Parallel to the evolving role of immune checkpoint inhibitors many people believe that using chemotherapy is coming to an end. Moreover laymen opinions are being communicated about the detrimental role of chemotherapy. The aim of this article is to dissolve this misbelief. The manuscript details the immunomodulatory effects of chemotherapy. Having the ability to stop division of cancer cells and kill them together with immunomodulatory effects, chemotherapy is an ideal partner for combination with immune checkpoint inhibitors. There is increasing number of evidence for synergistic effect between chemotherapy and immuno-oncology drugs. Ongoing and future clinical trials will determine the optimal combinations.


Assuntos
Antineoplásicos/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Antineoplásicos/efeitos adversos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Neoplasias/imunologia
14.
Nat Commun ; 10(1): 4298, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541102

RESUMO

Insecticidal fungi represent a promising alternative to chemical pesticides for disease vector control. Here, we show that the pathogenic fungus Beauveria bassiana exports a microRNA-like RNA (bba-milR1) that hijacks the host RNA-interference machinery in mosquito cells by binding to Argonaute 1 (AGO1). bba-milR1 is highly expressed during fungal penetration of the mosquito integument, and suppresses host immunity by silencing expression of the mosquito Toll receptor ligand Spätzle 4 (Spz4). Later, upon entering the hemocoel, bba-milR1 expression is decreased, which avoids induction of the host proteinase CLIPB9 that activates the melanization response. Thus, our results indicate that the pathogen deploys a cross-kingdom small-RNA effector that attenuates host immunity and facilitates infection.


Assuntos
Beauveria/imunologia , Interações Hospedeiro-Patógeno/imunologia , MicroRNAs/metabolismo , Mosquitos Vetores/imunologia , Mosquitos Vetores/microbiologia , Animais , Anopheles/imunologia , Anopheles/microbiologia , Beauveria/patogenicidade , Feminino , Perfilação da Expressão Gênica , Sistema Imunitário/imunologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Malária/imunologia , Controle Biológico de Vetores , Interferência de RNA , RNA de Cadeia Dupla
16.
Immunogenetics ; 71(8-9): 513-518, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31418051

RESUMO

Demonstration that immature CD4 + 8+ thymocytes contain T cell precursors that are subjected to positive and negative selection was the major step towards understanding how the adaptive immune system acquires the ability to distinguish foreign or abnormal (mutated or infected) self-cells from normal (healthy) cells. In the present review, the roles of TCR, CD4, CD8, and MHC molecules in intrathymic selection and some of the crucial experiments that contributed to the solution of the great immunological puzzle of self/nonself discrimination are described in an historical perspective. Recently, these experiments were highlighted by the immunological community by awarding the 2016 Novartis Prize for Immunology to Philippa Marrack, John Kappler, and Harald von Boehmer.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Doenças Autoimunes/imunologia , Sistema Imunitário/imunologia , Tolerância a Antígenos Próprios , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Animais , Humanos , Complexo Principal de Histocompatibilidade/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Timo/citologia
17.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412566

RESUMO

Immune cells play critical roles in tumor prevention as well as initiation and progression. However, immune-resistant cancer cells can evade the immune system and proceed to form tumors. The normal microenvironment (immune cells, fibroblasts, blood and lymphatic vessels, and interstitial extracellular matrix (ECM)) maintains tissue homeostasis and prevents tumor initiation. Inflammatory mediators, reactive oxygen species, cytokines, and chemokines from an altered microenvironment promote tumor growth. During the last decade, thyroid cancer, the most frequent cancer of the endocrine system, has emerged as the fifth most incident cancer in the United States (USA), and its incidence is steadily growing. Inflammation has long been associated with thyroid cancer, raising critical questions about the role of immune cells in its pathogenesis. A plethora of immune cells and their mediators are present in the thyroid cancer ecosystem. Monoclonal antibodies (mAbs) targeting immune checkpoints, such as mAbs anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed cell death protein-1/programmed cell death ligand-1 (anti-PD-1/PD-L1), have revolutionized the treatment of many malignancies, but they induce thyroid dysfunction in up to 10% of patients, presumably by enhancing autoimmunity. Combination strategies involving immune checkpoint inhibitors (ICIs) with tyrosine kinase (TK) or serine/threonine protein kinase B-raf (BRAF) inhibitors are showing considerable promise in the treatment of advanced thyroid cancer. This review illustrates how different immune cells contribute to thyroid cancer development and the rationale for the antitumor effects of ICIs in combination with BRAF/TK inhibitors.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Imunomodulação/efeitos dos fármacos , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Indutores da Angiogênese/metabolismo , Animais , Antineoplásicos Imunológicos/uso terapêutico , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Terapia de Alvo Molecular , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
18.
Nat Commun ; 10(1): 3298, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363098

RESUMO

Gastric acid suppression promotes allergy in mechanistic animal experiments and observational human studies, but whether gastric acid inhibitors increase allergy incidence at a population level remains uncharacterized. Here we aim to assess the use of anti-allergic medication following prescription of gastric acid inhibitors. We analyze data from health insurance records covering 97% of Austrian population between 2009 and 2013 on prescriptions of gastric acid inhibitors, anti-allergic drugs, or other commonly prescribed (lipid-modifying and antihypertensive) drugs as controls. Here we show that rate ratios for anti-allergic following gastric acid-inhibiting drug prescriptions are 1.96 (95%CI:1.95-1.97) and 3.07 (95%-CI:2.89-3.27) in an overall and regional Austrian dataset. These findings are more prominent in women and occur for all assessed gastric acid-inhibiting substances. Rate ratios increase from 1.47 (95%CI:1.45-1.49) in subjects <20 years, to 5.20 (95%-CI:5.15-5.25) in > 60 year olds. We report an epidemiologic relationship between gastric acid-suppression and development of allergic symptoms.


Assuntos
Antiulcerosos/efeitos adversos , Hipersensibilidade/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Adulto , Idoso , Antiulcerosos/uso terapêutico , Áustria/epidemiologia , Feminino , Ácido Gástrico/química , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Incidência , Masculino , Registros Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Adulto Jovem
19.
Clin Microbiol Rev ; 32(4)2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31366611

RESUMO

The skin is an organ harboring several types of immune cells that participate in innate and adaptive immune responses. The immune system of the skin comprises both skin cells and professional immune cells that together constitute what is designated skin-associated lymphoid tissue (SALT). In this review, I extensively discuss the organization of SALT and the mechanisms involved in its responses to infectious diseases of the skin and mucosa. The nature of these SALT responses, and the cellular mediators involved, often determines the clinical course of such infections. I list and describe the components of innate immunity, such as the roles of the keratinocyte barrier and of inflammatory and natural killer cells. I also examine the mechanisms involved in adaptive immune responses, with emphasis on new cytokine profiles, and the role of cell death phenomena in host-pathogen interactions and control of the immune responses to infectious agents. Finally, I highlight the importance of studying SALT in order to better understand host-pathogen relationships involving the skin and detail future directions in the immunological investigation of this organ, especially in light of recent findings regarding the skin immune system.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Sistema Imunitário/imunologia , Tecido Linfoide/imunologia , Dermatopatias/imunologia , Pele/imunologia , Humanos
20.
Curr Microbiol ; 76(11): 1278-1289, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446476

RESUMO

The homeostatic systems, such as the nervous and immune systems, show deterioration in aging as a consequence of the age-related oxidative-inflammatory stress establishment. The supplementation with fermented milk containing probiotic bacteria could be a good nutritional strategy to improve homeostatic system functions in aged individuals through the modulation of their redox state. The aim of the present study was to evaluate the effect of 2-week supplementation with a commercial fermented milk containing yogurt species (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus), and the probiotic Lactobacillus casei DN-114001 on behavior, redox state, and immune cell functions of aged mice as well as on their life span. Aged female ICR-CD1 mice were supplemented with fermented milk containing these probiotics for 2 weeks. After this period, a variety of behavioral tests were performed and several parameters of redox state and function of peritoneal leukocytes were analyzed. The results showed that the 2-week supplementation of fermented milk containing probiotics improved behavior (such as muscular vigor, exploratory activity, and anxiety-like behavior) as well as the redox state and functions of peritoneal immune cells in aged mice. In conclusion, the present study shows that the supplementation with fermented milk containing probiotics for a short period of time could be a good nutritional strategy to promote healthy aging.


Assuntos
Envelhecimento/imunologia , Envelhecimento/psicologia , Sistema Imunitário/efeitos dos fármacos , Probióticos/administração & dosagem , Iogurte/microbiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Humanos , Sistema Imunitário/imunologia , Lactobacillus casei/fisiologia , Lactobacillus delbrueckii/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Oxirredução/efeitos dos fármacos , Streptococcus thermophilus/fisiologia , Iogurte/análise
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