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Migration and homeostasis of regulatory T cells in rheumatoid arthritis

Regulatory T (T(reg)) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of T(reg) cel...

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Autores principales: Kotschenreuther, Konstantin, Yan, Shuaifeng, Kofler, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398455/
https://www.ncbi.nlm.nih.gov/pubmed/36016949
http://dx.doi.org/10.3389/fimmu.2022.947636
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author Kotschenreuther, Konstantin
Yan, Shuaifeng
Kofler, David M.
author_facet Kotschenreuther, Konstantin
Yan, Shuaifeng
Kofler, David M.
author_sort Kotschenreuther, Konstantin
collection PubMed
description Regulatory T (T(reg)) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of T(reg) cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. T(reg) cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of T(reg) cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in T(reg) cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of T(reg) cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced T(reg) cell trafficking. Another protein which facilitates T(reg) cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in T(reg) cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of T(reg) cell migration and review the current knowledge about impaired T(reg) cell homeostasis in RA.
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spelling pubmed-93984552022-08-24 Migration and homeostasis of regulatory T cells in rheumatoid arthritis Kotschenreuther, Konstantin Yan, Shuaifeng Kofler, David M. Front Immunol Immunology Regulatory T (T(reg)) cells are garnering increased attention in research related to autoimmune diseases, including rheumatoid arthritis (RA). They play an essential role in the maintenance of immune homeostasis by restricting effector T cell activity. Reduced functions and frequencies of T(reg) cells contribute to the pathogenesis of RA, a common autoimmune disease which leads to systemic inflammation and erosive joint destruction. T(reg) cells from patients with RA are characterized by impaired functions and by an altered phenotype. They show increased plasticity towards Th17 cells and a reduced suppressive capacity. Besides the suppressive function of T(reg) cells, their effectiveness is determined by their ability to migrate into inflamed tissues. In the past years, new mechanisms involved in T(reg) cell migration have been identified. One example of such a mechanism is the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Efficient migration of T(reg) cells requires the presence of VASP. IL-6, a cytokine which is abundantly present in the peripheral blood and in the synovial tissue of RA patients, induces posttranslational modifications of VASP. Recently, it has been shown in mice with collagen-induced arthritis (CIA) that this IL-6 mediated posttranslational modification leads to reduced T(reg) cell trafficking. Another protein which facilitates T(reg) cell migration is G-protein-signaling modulator 2 (GPSM2). It modulates G-protein coupled receptor functioning, thereby altering the cellular activity initiated by cell surface receptors in response to extracellular signals. The almost complete lack of GPSM2 in T(reg) cells from RA patients contributes to their reduced ability to migrate towards inflammatory sites. In this review article, we highlight the newly identified mechanisms of T(reg) cell migration and review the current knowledge about impaired T(reg) cell homeostasis in RA. Frontiers Media S.A. 2022-08-09 /pmc/articles/PMC9398455/ /pubmed/36016949 http://dx.doi.org/10.3389/fimmu.2022.947636 Text en Copyright © 2022 Kotschenreuther, Yan and Kofler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Kotschenreuther, Konstantin
Yan, Shuaifeng
Kofler, David M.
Migration and homeostasis of regulatory T cells in rheumatoid arthritis
title Migration and homeostasis of regulatory T cells in rheumatoid arthritis
title_full Migration and homeostasis of regulatory T cells in rheumatoid arthritis
title_fullStr Migration and homeostasis of regulatory T cells in rheumatoid arthritis
title_full_unstemmed Migration and homeostasis of regulatory T cells in rheumatoid arthritis
title_short Migration and homeostasis of regulatory T cells in rheumatoid arthritis
title_sort migration and homeostasis of regulatory t cells in rheumatoid arthritis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398455/
https://www.ncbi.nlm.nih.gov/pubmed/36016949
http://dx.doi.org/10.3389/fimmu.2022.947636
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