Migration and homeostasis of regulatory T cells in rheumatoid arthritis

Konstantin Kotschenreuther; Shuaifeng Yan; David M Kofler

doi:10.3389/fimmu.2022.947636

Migration and homeostasis of regulatory T cells in rheumatoid arthritis

Front Immunol. 2022 Aug 9:13:947636. doi: 10.3389/fimmu.2022.947636. eCollection 2022.

Authors

Konstantin Kotschenreuther¹, Shuaifeng Yan¹, David M Kofler^{1

2}

Affiliations

¹ Laboratory of Molecular Immunology, Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
² Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.

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.

Keywords: T cell homeostasis; T cell migration; Treg - regulatory T cells; collagen-induced arthritis (CIA); rheumatoid arthritis.

Publication types

Review

MeSH terms

Animals
Arthritis, Rheumatoid*
Homeostasis
Interleukin-6 / metabolism
Mice
Mice, Inbred DBA
T-Lymphocytes, Regulatory*

Substances

Interleukin-6