Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.196
Filtrar
2.
Int J Mol Sci ; 22(15)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34361107

RESUMO

Chemotactic cytokines-chemokines-control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body's defense system. Many chemokines also participate in pathological processes leading up to and exacerbating the inflammatory state characterizing chronic inflammatory diseases. In this review, we discuss the role of dendritic cells (DCs) and the central chemokine receptor CCR7 in the initiation and sustainment of selected chronic inflammatory diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. We revisit the binary role that CCR7 plays in combatting and progressing cancer, and we discuss how CCR7 and DCs can be harnessed for the treatment of cancer. To provide the necessary background, we review the differential roles of the natural ligands of CCR7, CCL19, and CCL21 and how they direct the mobilization of activated DCs to lymphoid organs and control the formation of associated lymphoid tissues (ALTs). We provide an overview of DC subsets and, briefly, elaborate on the different T-cell effector types generated upon DC-T cell priming. In the conclusion, we promote CCR7 as a possible target of future drugs with an antagonistic effect to reduce inflammation in chronic inflammatory diseases and an agonistic effect for boosting the reactivation of the immune system against cancer in cell-based and/or immune checkpoint inhibitor (ICI)-based anti-cancer therapy.


Assuntos
Doenças Autoimunes/patologia , Células Dendríticas/imunologia , Inflamação/patologia , Neoplasias/patologia , Receptores CCR7/metabolismo , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Neoplasias/imunologia , Neoplasias/metabolismo , Transdução de Sinais
3.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360810

RESUMO

Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most efficient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this review has elucidated the general aspects of DCs as well as the current dynamic perspectives and distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, cat, horse, cattle, sheep, pig, and non-human primates. Besides the role that DCs play in immune response, they also play a pathogenic role in many diseases, thus becoming a target in disease prevention and treatment. In addition, its roles in clinical immunology have also been addressed, which include its involvement in transplantation, autoimmune disease, viral infections, cancer, and as a vaccine target. Therefore, based on the current knowledge and understanding of the important roles they play, DCs can be used in the future as a powerful tool for manipulating the immune system.


Assuntos
Células Dendríticas/imunologia , Animais , Doenças Autoimunes/imunologia , Células Dendríticas/citologia , Humanos , Neoplasias/imunologia , Viroses/imunologia
4.
FEBS J ; 288(16): 4728-4729, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398531

RESUMO

With the current issue of The FEBS Journal, we are introducing a new category of invited review article contributions on Emerging Methods and Technologies. These articles provide an overview and discussion of recent, emerging methods that significantly advance and improve research efforts in the different fields of molecular and cellular research of our The FEBS Journal authors and readers. Deputy Editorial Manager Manuel Breuer and our Emerging Methods and Technologies Commissioning Editor Eric Chevet introduce the series.


Assuntos
Doenças Autoimunes/imunologia , Proteínas de Membrana/metabolismo , Neoplasias/imunologia , Polietilenotereftalatos/metabolismo , Polissacarídeos/imunologia , Humanos , Proteínas de Membrana/análise , Neoplasias/terapia , Polissacarídeos/química
5.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445670

RESUMO

While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body's adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.


Assuntos
Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , COVID-19/imunologia , Imunidade Adaptativa , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade , COVID-19/virologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , SARS-CoV-2/imunologia
7.
Nat Immunol ; 22(9): 1163-1174, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34426690

RESUMO

The immunosuppressive function of regulatory T (Treg) cells is dependent on continuous expression of the transcription factor Foxp3. Foxp3 loss of function or induced ablation of Treg cells results in a fatal autoimmune disease featuring all known types of inflammatory responses with every manifestation stemming from Treg cell paucity, highlighting a vital function of Treg cells in preventing fatal autoimmune inflammation. However, a major question remains whether Treg cells can persist and effectively exert their function in a disease state, where a broad spectrum of inflammatory mediators can either inactivate Treg cells or render innate and adaptive pro-inflammatory effector cells insensitive to suppression. By reinstating Foxp3 protein expression and suppressor function in cells expressing a reversible Foxp3 null allele in severely diseased mice, we found that the resulting single pool of rescued Treg cells normalized immune activation, quelled severe tissue inflammation, reversed fatal autoimmune disease and provided long-term protection against them. Thus, Treg cells are functional in settings of established broad-spectrum systemic inflammation and are capable of affording sustained reset of immune homeostasis.


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Fatores de Transcrição Forkhead/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Linfócitos T Reguladores/imunologia , Animais , Autoimunidade/genética , Diferenciação Celular/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica/genética , Homeostase/imunologia , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Resposta Inflamatória Sistêmica/patologia
9.
Pharmacol Res ; 171: 105786, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34314858

RESUMO

Women of childbearing age are largely affected by several autoimmune disorders (the estimates range between 1.5 and 10 per 10,000). The increasing number of effective biological agents has dramatically revolutionized the treatment of these clinical conditions, ameliorating the patient's quality of life. The use of these agents by women during pregnancy is growing to ensure the disease activity control and avoid adverse health outcomes. However, for many newer biological agents, the degree of information concerning their use in pregnancy is often incomplete to perform a conclusive risk assessment on fetal and maternal health given the exclusion of this specific population from pharmacological clinical trials. More recently, the COVID-19 pandemic has confirmed the unacceptable inequities of pharmacological research and medical treatment for pregnant and lactating women, exacerbating the need for filling the gaps of quantitative and qualitative pharmacology data in this sensitive population. ere we summarize (i) what is already known about safety and effectiveness of biological agents in this understudied population (with specific focus on pregnancy-related health outcomes), and what we are going to learn from the on-going studies among pregnant women treated with biological agents; (ii) the methodological and ethical considerations that characterize the pharmacological research in pregnancy, also discussing emerging evidence on the use of therapeutic drug monitoring (TDM) in this clinical setting.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Gestantes , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/imunologia , Resultado da Gravidez/epidemiologia
10.
Mol Immunol ; 137: 105-113, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242919

RESUMO

Underlying mechanisms of multi-organ manifestations and exacerbated inflammation in COVID-19 are yet to be delineated. The hypothesis of SARS-CoV-2 triggering autoimmunity is gaining attention and, in the present study, we have identified 28 human proteins harbouring regions homologous to SARS-CoV-2 peptides that could possibly be acting as autoantigens in COVID-19 patients displaying autoimmune conditions. Interestingly, these conserved regions are amongst the experimentally validated B cell epitopes of SARS-CoV-2 proteins. The reported human proteins have demonstrated presence of autoantibodies against them in typical autoimmune conditions which may explain the frequent occurrence of autoimmune conditions following SARS-CoV-2 infection. Moreover, the proposed autoantigens' widespread tissue distribution is suggestive of their involvement in multi-organ manifestations via molecular mimicry. We opine that our report may aid in directing subsequent necessary antigen-specific studies, results of which would be of long-term relevance in management of extrapulmonary symptoms of COVID-19.


Assuntos
Autoantígenos/imunologia , Doenças Autoimunes/complicações , COVID-19/etiologia , Epitopos de Linfócito B/imunologia , SARS-CoV-2/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , Autoimunidade/imunologia , COVID-19/imunologia , COVID-19/patologia , Humanos , Mimetismo Molecular/imunologia
11.
J Autoimmun ; 123: 102687, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311142

RESUMO

The impact of SARS-CoV-2 infection in patients with autoimmune/auto-inflammatory rheumatic diseases (AARD) under immunomodulatory treatment has been a focus of interest during the COVID-19 pandemic. In this observational study, demographic data, disease related features and comorbidities, COVID-19 manifestations and outcome as well as antibody responses to SARS-CoV-2 were recorded among 77 consecutive patients with underlying AARD infected by SARS-CoV-2. Analysis of data was performed using univariate and multivariate models. Most patients (68.8%) had a mild COVID-19 course. The predominant clinical manifestations were fatigue (58.4%), low grade fever (45.4%) and upper respiratory tract symptoms (68.8%). About a quarter of patients required hospitalization (23.3%) and the mortality rate was 1.3%. Regarding COVID-19 severity, prior treatment with corticosteroids, mycophenolate mofetil or rituximab was more common in patients who developed a more serious disease course (60.0 vs 29.9%, p = 0.003, 40.0 vs 7.5%, p = 0.003, 10.0 vs 0.0%, p = 0.009, respectively). When disease related features and comorbidities were considered in multivariate models, older age and lung disease in the context of the AARD were found to be independent predictive factors for hospitalization (OR [95%]: 1.09 [1.03-1.15] and 6.43 [1.11-37.19]). Among COVID-19 related features, patients with shortness of breath and high-grade fever were more likely to get hospitalized (OR [95%]: 7.06 [1.36-36.57], 12.04 [2.96-48.86]), while anosmia was independently associated with lower hospitalization risk (OR [95%]: 0.09 [0.01-0.99]). Though the majority of AARD patients displayed a mild COVID-19 course, certain underlying disease features and COVID-19 related manifestations should prompt alertness for the physician to identify patients with AARD at high risk for severe COVID-19 and need for hospitalization.


Assuntos
Doenças Autoimunes/epidemiologia , COVID-19/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/biossíntese , Infecções Assintomáticas/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Comorbidade , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/imunologia , Estado Terminal , Feminino , Grécia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Hipotireoidismo/epidemiologia , Hospedeiro Imunocomprometido , Imunoglobulina G/biossíntese , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Literatura de Revisão como Assunto , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Avaliação de Sintomas
12.
Front Immunol ; 12: 686462, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276672

RESUMO

Immune homeostasis is disturbed during severe viral infections, which can lead to loss of tolerance to self-peptides and result in short- or long-term autoimmunity. Using publicly available transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 52 autoantigens, known to be associated with 24 autoimmune diseases, during SAR-CoV-2 infection. Seven autoantigens (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) were upregulated in whole blood samples. MPO and TSHR were overexpressed in both lung autopsies and whole blood tissue and were associated with more severe COVID-19. Neutrophil activation derived autoantigens (MPO, PRTN3, and PADI4) were prominently increased in blood of both SARS-CoV-1 and SARS-CoV-2 viral infections, while TSHR and PTPRN2 autoantigens were specifically increased in SARS-CoV-2. Using single-cell dataset from peripheral blood mononuclear cells (PBMCs), we observed an upregulation of MPO, PRTN3, and PADI4 autoantigens within the low-density neutrophil subset. To validate our in-silico analysis, we measured plasma protein levels of two autoantigens, MPO and PRTN3, in severe and asymptomatic COVID-19. The protein levels of these two autoantigens were significantly upregulated in more severe COVID-19 infections. In conclusion, the immunopathology and severity of COVID-19 could result in transient autoimmune activation. Longitudinal follow-up studies of confirmed cases of COVID-19 could determine the enduring effects of viral infection including development of autoimmune disease.


Assuntos
Autoantígenos/genética , Autoimunidade/genética , COVID-19/imunologia , SARS-CoV-2/imunologia , Transcriptoma , Doenças Assintomáticas , Autoantígenos/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Simulação por Computador , Bases de Dados Genéticas , Humanos , Pulmão/patologia , Mieloblastina/sangue , Mieloblastina/genética , Ativação de Neutrófilo , Neutrófilos/imunologia , Peroxidase/sangue , Peroxidase/genética , RNA-Seq , Índice de Gravidade de Doença , Regulação para Cima/genética
13.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299252

RESUMO

Neutrophils and their extracellular traps have been shown to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the detailed mechanisms in joints are still unclear, and their regulation remains to be solved. Here, we explored neutrophil extracellular trap (NET)osis in experimental models of arthritis and further investigated the effects of interleukin-6 (IL-6) inhibition in neutrophils and NETosis. In skins of peptide GPI-induced arthritis (pGIA), citrullinated protein was detected as well as citrullinated histone expression in immunized skin but this was not specific to pGIA. Citrullinated histone expression in pGIA joints was specific to pGIA and was merged with neutrophil elastase, suggesting NETosis. Neutrophils in joints tend to upregulate IL-6 receptors when compared with bone marrow neutrophils. Administration of mouse anti-IL-6 receptor antibodies in pGIA suppressed arthritis in association with a decrease in neutrophil infiltration and NETosis in joints. In the plasma of RA patients, citrullinated protein was significantly reduced after tocilizumab treatment. Our results suggest that IL-6 enhances neutrophil chemotaxis and NETosis in inflammatory joints and could be the source of citrullinated proteins.


Assuntos
Artrite Reumatoide/imunologia , Armadilhas Extracelulares/metabolismo , Interleucina-6/metabolismo , Animais , Artrite Reumatoide/metabolismo , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Citrulina/metabolismo , Armadilhas Extracelulares/genética , Armadilhas Extracelulares/fisiologia , Histonas/metabolismo , Interleucina-6/imunologia , Articulações/imunologia , Elastase de Leucócito/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , Neutrófilos/metabolismo , Receptores de Interleucina-6/metabolismo
14.
FASEB J ; 35(7): e21746, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151465

RESUMO

Bullous pemphigoid (BP), an autoimmune skin disease, is characterized by autoantibodies against hemidesmosomal proteins in the skin and mucous membranes. Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno-inflammatory consequences. In the present study, we found that circulating NET-related biomarker levels increased in serum and blister fluid of BP patients and significantly correlated with disease severity. Additionally, circulating neutrophils from BP patients displayed enhanced spontaneous NETs formation than healthy controls. In vitro, BP180-NC16A immune complexes-induced NETosis in neutrophils from BP patients, which was abrogated by Fcγ receptor and/or NADPH pathway blockade. Furthermore, the elevated levels of NETs from BP patients boosted autoantibody production by inducing B-cell differentiation into plasma cells, mediated by MAPK P38 cascade activation. Together, our findings provide strong evidence that NETs are involved in a pathogenic loop, causing excessive differentiation of B cells and promotion of autoantibody production. Hence, targeting aberrant neutrophil responses will provide novel potential targets for the treatment of BP.


Assuntos
Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Diferenciação Celular/imunologia , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Penfigoide Bolhoso/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Linfócitos B/metabolismo , Biomarcadores/metabolismo , Vesícula/imunologia , Vesícula/metabolismo , Armadilhas Extracelulares/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Neutrófilos/metabolismo , Penfigoide Bolhoso/metabolismo , Plasmócitos/imunologia , Plasmócitos/metabolismo , Receptores de IgG/imunologia , Transdução de Sinais/imunologia , Pele/imunologia , Pele/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Adv Protein Chem Struct Biol ; 126: 39-62, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34090619

RESUMO

Mesenchymal stem cells (MSC) are adult stem cells which reside in almost all postnatal tissue where, in juxtacrine and paracrine manner, regulate phenotype and function of immune cells, maintain tissue homeostasis, attenuate on-going inflammation and promote repair and regeneration of injured tissues. Due to their capacity to suppress detrimental immune response, MSC have been considered as potentially new therapeutic agents in the treatment of autoimmune and inflammatory diseases. It was recently revealed that apoptosis may increase anti-inflammatory properties of MSC by enhancing their capacity to induce generation of immunosuppressive phenotype in macrophages and dendritic cells. Upon phagocytosis, apoptotic MSC induce generation of immunosuppressive phenotype in monocytes/macrophages and promote production of anti-inflammatory cytokines and growth factors that attenuate inflammation and facilitate repair and regeneration of injured tissues. Importantly, immunomodulation mediated by apoptotic MSC was either similar or even better than immunomodulation accomplished by viable MSC. In contrast to viable MSC, which obtain either pro- or anti-inflammatory phenotype upon engraftment in different tissue microenvironments, apoptotic MSC were not subject to changes in their immunomodulatory characteristics upon diverse stimuli, indicating their potential for clinical use. In this chapter, we summarized current knowledge about beneficial effects of apoptotic MSC in the suppression of detrimental local and systemic immune response, and we emphasized their therapeutic potential in the treatment of inflammatory diseases.


Assuntos
Apoptose/imunologia , Doenças Autoimunes/imunologia , Tolerância Imunológica , Células-Tronco Mesenquimais/imunologia , Animais , Doenças Autoimunes/terapia , Humanos , Inflamação/imunologia , Inflamação/terapia , Macrófagos/imunologia , Monócitos/imunologia , Comunicação Parácrina/imunologia , Fagocitose
16.
Methods Mol Biol ; 2344: 99-106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34115354

RESUMO

Autoantibodies are humoral antibodies against self-proteins and play vital roles in maintaining the homeostasis. Autoantibodies can also target posttranslational modifications (PTMs) of proteins and the identification of new PTM autoantibodies is important to identify biomarkers for the early diagnosis of cancer and autoimmune diseases. In this chapter, we describe a method to detect PTM autoantibodies using citrullinated peptide microarray as an example. This method can be used to screen serum autoantibodies for different human diseases.


Assuntos
Autoanticorpos/análise , Doenças Autoimunes/diagnóstico , Análise Serial de Proteínas , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Biomarcadores/análise , Humanos , Processamento de Proteína Pós-Traducional
17.
Int Immunopharmacol ; 96: 107761, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162139

RESUMO

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.


Assuntos
Doenças Autoimunes/terapia , Doença Crônica/terapia , Inflamação/terapia , Linfócitos T Reguladores/fisiologia , Vacinas/imunologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Doenças Autoimunes/imunologia , Humanos , Fatores Imunológicos/farmacologia , Imunomodulação/fisiologia , Imunossupressores/farmacologia , Inflamação/imunologia , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Vacinação
18.
Exp Dermatol ; 30(9): 1254-1257, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34081788

RESUMO

The SARS-CoV-2 pandemic has evolved to a global health problem with a dramatic morbidity and mortality rate impacting our daily life and those of many patients. While there is evidence that some diseases are associated with an increased risk for development of a more severe course of COVID-19, little is known on protective conditions. Importantly, clearance of viral infection and protection against disease manifestation crucially depends on functional innate and adaptive immunity and the interferon signalling axis. Here, we hypothesize that patients with non-segmental vitiligo (NSV), an autoimmune skin (and mucosal) disorder, may clear SARS-CoV-2 infection more efficiently and have a lower risk of COVID-19 development. Conversely, in case of COVID-19 development, vitiligo autoimmunity may influence the cytokine storm-related disease burden. In addition, immune activation during SARS-CoV-2 infection or COVID-19 disease might increase vitiligo disease activity. Our hypothesis is based on the shift of the immune system in NSV towards adaptive type 1 (IFNγ and CD8 T cells) and innate immune responses. Identified susceptibility genes of NSV patients may further confer increased antiviral activity. To validate our hypothesis, we suggest an international consortium to perform a retrospective data registry and patient-reported study on a large number of NSV patients worldwide during the COVID-19 pandemic.


Assuntos
Doenças Autoimunes/epidemiologia , COVID-19/epidemiologia , Vitiligo/epidemiologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , COVID-19/complicações , COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Predisposição Genética para Doença , Humanos , Imunidade Inata , Fatores de Proteção , SARS-CoV-2 , Vitiligo/genética , Vitiligo/imunologia
19.
Nat Immunol ; 22(7): 809-819, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34140679

RESUMO

CD8+ T cells are critical mediators of cytotoxic effector function in infection, cancer and autoimmunity. In cancer and chronic viral infection, CD8+ T cells undergo a progressive loss of cytokine production and cytotoxicity, a state termed T cell exhaustion. In autoimmunity, autoreactive CD8+ T cells retain the capacity to effectively mediate the destruction of host tissues. Although the clinical outcome differs in each context, CD8+ T cells are chronically exposed to antigen in all three. These chronically stimulated CD8+ T cells share some common phenotypic features, as well as transcriptional and epigenetic programming, across disease contexts. A better understanding of these CD8+ T cell states may reveal novel strategies to augment clearance of chronic viral infection and cancer and to mitigate self-reactivity leading to tissue damage in autoimmunity.


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade , Linfócitos T CD8-Positivos/imunologia , Doenças Transmissíveis/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Doença Crônica , Doenças Transmissíveis/genética , Doenças Transmissíveis/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Epigênese Genética , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Fenótipo , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais
20.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073458

RESUMO

Cytotoxic CD4+ T cells (CD4 CTL) are terminally differentiated T helper cells that contribute to autoimmune diseases, such as multiple sclerosis. We developed a novel triple co-culture transwell assay to study mutual interactions between CD4 CTL, conventional TH cells, and regulatory T cells (Tregs) simultaneously. We show that, while CD4 CTL are resistant to suppression by Tregs in vitro, the conditioned medium of CD4 CTL accentuates the suppressive phenotype of Tregs by upregulating IL-10, Granzyme B, CTLA-4, and PD-1. We demonstrate that CD4 CTL conditioned medium skews memory TH cells to a TH17 phenotype, suggesting that the CD4 CTL induce bystander polarization. In our triple co-culture assay, the CD4 CTL secretome promotes the proliferation of TH cells, even in the presence of Tregs. However, when cell-cell contact is established between CD4 CTL and TH cells, the proliferation of TH cells is no longer increased and Treg-mediated suppression is restored. Taken together, our results suggest that when TH cells acquire cytotoxic properties, these Treg-resistant CD4 CTL affect the proliferation and phenotype of conventional TH cells in their vicinity. By creating such a pro-inflammatory microenvironment, CD4 CTL may favor their own persistence and expansion, and that of other potentially pathogenic TH cells, thereby contributing to pathogenic responses in autoimmune disorders.


Assuntos
Doenças Autoimunes/imunologia , Proliferação de Células , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Antígeno CTLA-4/imunologia , Feminino , Granzimas/imunologia , Humanos , Interleucina-10/imunologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Reguladores/citologia , Células Th17/citologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...