T-cell immunoglobulin and mucin domain 3 is upregulated in rheumatoid arthritis, but insufficient in controlling inflammation

• Published in: American journal of clinical and experimental immunology Vol. 11; no. 3; pp. 34 - 44
• Main Authors: Skejoe, Caecilie, Hansen, Aida S, Stengaard-Pedersen, Kristian, Junker, Peter, Hoerslev-Pedersen, Kim, Hetland, Merete L, Oestergaard, Mikkel, Greisen, Stinne, Hvid, Malene, Deleuran, Mette, Deleuran, Bent
• Format: Journal Article
• Language: English
• Published: e-Century Publishing Corporation 01.01.2022
• Subjects: Original
• ISSN: 2164-7712; 2164-7712

OBJECTIVESRheumatoid arthritis (RA) is a chronic autoimmune disease, that involves both pro- and anti-inflammatory mechanisms. The purpose of the present study is to investigate T-cell immunoglobulin and mucin domain 3 (Tim-3) in RA. METHODSPlasma levels of soluble (s) Tim-3 in early RA (n=98), were followed, to evaluate association with treatment and disease activity, acquired from a prospective collected biobank (clinicaltrials.gov (NCT00660647)). We also investigate the influence of Tim-3 on spontaneous cytokine production in synovial fluid mononuclear cells (SFMC) from RA patients after addition of neutralizing anti-Tim-3's antibodies, either alone or in combination with neutralizing anti-Programmed Cell death protein 1 (PD-1) antibodies. RESULTSLong-time stimulated CD4 T-cells expressed high levels of Tim-3, but tended to decrease their PD-1 expression. Tim-3 expression was exclusively seen co-expressed with PD-1 by CD3, CD4, CD45RO positive cells in the inflamed RA joint. Addition of neutralizing Tim-3 antibodies increased the secretion of IFNγ and MCP-1, in SFMC cultures from RA. Whereas neutralizing anti-PD-1 antibodies showed a broader impact on cytokine production. Finally, we observed that soluble Tim-3 is increased in plasma and is associated with disease activity in early RA. CONCLUSIONTaken together, our findings indicate disease-suppressive functions of Tim-3 in RA.