Resistin gene expression is downregulated in CD4⁺ T helper lymphocytes and CD14⁺ monocytes in rheumatoid arthritis responding to TNF-α inhibition

Rheumatoid arthritis (RA) is caused by complex interactions between immune cells and sustained by Th1 response cytokines. Resistin (resistance to insulin) (RETN) is an inflammatory cytokine, first discovered in murine adipocytes. In man RETN is mainly secreted by monocytes. The distinct role of RETN in the immune reaction is uncertain, however RETN has pro-inflammatory, pro-fibrotic and possibly tolerogenic properties. The aim was to assess the reaction of RETN gene expression to TNFα inhibition (I) in pathogenetic immune cell subsets in RA, in the context of Th1-, inflammatory- and regulatory cytokine gene expressions. Accordingly, we measured RETN, IFNγ, TNFβ, IL-1β, TNFα, TGFβ and IL-10 gene expressions in CD14(+) monocytes, CD4(+) T helper (Th) lymphocytes (ly), CD8(+) T cytotoxic (Tc) ly and CD19(+) B ly in active RA before and three months after start of TNFαI. Leukocyte subsets were separated by specific monoclonal antibody covered beads, RNA extracted and levels of RETN, Th1 response-, inflammatory and regulatory cytokine mRNAs measured by RT-qPCR technique. We found that TNFαI caused a significant downregulation of RETN gene expression in CD14(+) monocytes and CD4(+) Th ly and was unchanged in CD8(+) Tc ly and CD19(+) B ly. Both in active RA and during TNFαI, RETN mRNA levels were significantly higher in CD14(+) monocytes than in all other examined cell types. In monocytes, fold change in RETN and TGFβ gene expressions upon TNFαI correlated significantly. Our findings indicate that RETN has pro-inflammatory as well as proresolving roles in active RA. This article is protected by copyright. All rights reserved.