Mechanisms of human FoxP3+ Treg cell development and function in health and disease
| العنوان: | Mechanisms of human FoxP3+ Treg cell development and function in health and disease |
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| المؤلفون: | T Al-Aubodah, Ciriaco A. Piccirillo, M Attias |
| المصدر: | Clinical and Experimental Immunology |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Review Article, medicine.disease_cause, T-Lymphocytes, Regulatory, regulatory T cells, Epigenesis, Genetic, Autoimmunity, Arthritis, Rheumatoid, Translational Research, Biomedical, Cell therapy, 0302 clinical medicine, Neoplasms, Immunology and Allergy, IL-2 receptor, Review Articles, education.field_of_study, Effector, Peripheral tolerance, FOXP3, Cell Differentiation, Forkhead Transcription Factors, Genetic Diseases, X-Linked, hemic and immune systems, Review Series: Regulatory T Cells, Immune System Diseases, Immunotherapy, Signal Transduction, Diarrhea, Immunology, Population, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, Biology, 03 medical and health sciences, Series Editor: Ciriaco A. Piccirillo, medicine, Humans, Cell Lineage, education, Transcription factor, Inflammation, human immunology, Peripheral Tolerance, Models, Immunological, regulatory T cell dysfunction, Diabetes Mellitus, Type 1, 030104 developmental biology, antigen specificity, cell therapy, 030215 immunology |
| الوصف: | Summary Regulatory T (Treg) cells represent an essential component of peripheral tolerance. Given their potently immunosuppressive functions that is orchestrated by the lineage-defining transcription factor forkhead box protein 3 (FoxP3), clinical modulation of these cells in autoimmunity and cancer is a promising therapeutic target. However, recent evidence in mice and humans indicates that Treg cells represent a phenotypically and functionally heterogeneic population. Indeed, both suppressive and non-suppressive Treg cells exist in human blood that are otherwise indistinguishable from one another using classical Treg cell markers such as CD25 and FoxP3. Moreover, murine Treg cells display a degree of plasticity through which they acquire the trafficking pathways needed to home to tissues containing target effector T (Teff) cells. However, this plasticity can also result in Treg cell lineage instability and acquisition of proinflammatory Teff cell functions. Consequently, these dysfunctional CD4+FoxP3+ T cells in human and mouse may fail to maintain peripheral tolerance and instead support immunopathology. The mechanisms driving human Treg cell dysfunction are largely undefined, and obscured by the scarcity of reliable immunophenotypical markers and the disregard paid to Treg cell antigen-specificity in functional assays. Here, we review the mechanisms controlling the stability of the FoxP3+ Treg cell lineage phenotype. Particular attention will be paid to the developmental and functional heterogeneity of human Treg cells, and how abrogating these mechanisms can lead to lineage instability and Treg cell dysfunction in diseases like immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, type 1 diabetes, rheumatoid arthritis and cancer. |
| تدمد: | 1365-2249 0009-9104 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef58b6a8da846345f02202977e048e82Test https://doi.org/10.1111/cei.13290Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ef58b6a8da846345f02202977e048e82 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652249 00099104 |
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