Universität zu Köln

Kotschenreuther, Konstantin ORCID: 0000-0001-9455-2444, Yan, Shuaifeng and Kofler, David M. (2022). Migration and homeostasis of regulatory T cells in rheumatoid arthritis. Front. Immunol., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kotschenreuther, Konstantin UNSPECIFIED orcid.org/0000-0001-9455-2444 UNSPECIFIED Yan, Shuaifeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Kofler, David M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-663294
DOI:	10.3389/fimmu.2022.947636
Journal or Publication Title:	Front. Immunol.
Volume:	13
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLLAGEN-INDUCED ARTHRITIS; GROWTH-FACTOR-BETA; CHEMOATTRACTANT PROTEIN-1 MCP-1; TGF-BETA; AUTOIMMUNE-DISEASE; FOXP3 EXPRESSION; GENE-EXPRESSION; TNF-ALPHA; SYNOVIAL FIBROBLASTS; ADHESION MOLECULES Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66329