Meyer, Anja ORCID: 0000-0001-9904-5070, Yan, Shuaifeng, Golumba-Nagy, Viktoria, Esser, Ruth L., Barbarino, Verena, Blakemore, Stuart J., Rusyn, Lisa, Nikiforov, Anastasia, Seeger-Nukpezah, Tamina, Gruell, Holger, Pallasch, Christian P. and Kofler, David M. (2021). Kinase activity profiling reveals contribution of G-protein signaling modulator 2 deficiency to impaired regulatory T cell migration in rheumatoid arthritis. J. Autoimmun., 124. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1095-9157

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Abstract

The ability of regulatory T (T-reg) cells to migrate into inflammatory sites is reduced in autoimmune diseases, including rheumatoid arthritis (RA). The reasons for impaired Treg cell migration remain largely unknown. We performed multiplex human kinase activity arrays to explore possible differences in the post-translational phosphorylation status of kinase related proteins that could account for altered Treg cell migration in RA. Results were verified by migration assays and Western blot analysis of CD4+ T cells from RA patients and from mice with collagen type II induced arthritis. Kinome profiling of CD4+ T cells from RA patients revealed significantly altered post-translational phosphorylation of kinase related proteins, including G-protein-signaling modulator 2 (GPSM2), protein tyrosine kinase 6 (PTK6) and vitronectin precursor (VTNC). These proteins have not been associated with RA until now. We found that GPSM2 expression is reduced in CD4+ T cells from RA patients and is significantly downregulated in experimental autoimmune arthritis following immunization of mice with collagen type II. Interestingly, GPSM2 acts as a promoter of Treg cell migration in healthy individuals. Treatment of RA patients with interleukin-6 receptor (IL-6R) blocking antibodies restores GPSM2 expression, thereby improving Treg cell migration. Our study highlights the potential of multiplex kinase activity arrays as a tool for the identification of RA-related proteins which could serve as targets for novel treatments.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Meyer, AnjaUNSPECIFIEDorcid.org/0000-0001-9904-5070UNSPECIFIED
Yan, ShuaifengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Golumba-Nagy, ViktoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Esser, Ruth L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barbarino, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blakemore, Stuart J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rusyn, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikiforov, AnastasiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seeger-Nukpezah, TaminaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruell, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pallasch, Christian P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kofler, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-571095
DOI: 10.1016/j.jaut.2021.102726
Journal or Publication Title: J. Autoimmun.
Volume: 124
Date: 2021
Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication: LONDON
ISSN: 1095-9157
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; CLASSIFICATION CRITERIA; INTERLEUKIN-6; EXPRESSION; PATHWAYS; TOCILIZUMAB; RESISTANCE; INHIBITION; VIVOMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/57109

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