Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice

Abstract

Objectives: Suppressor of TCR signaling-2 (STS-2) is one of the RA susceptibility genes identified in genome-wide association studies (GWAS). We tried to verify the involvement of STS-2 on the development of autoimmune arthritis in a mouse model.

Methods: STS-2 knock-out (KO) and wild type (WT) mice were immunized with chicken type II collagen (CII). For CD4⁺ helper T cell (Th) subset analysis, intracellular cytokines in splenocytes and lymph node cells were stained and analyzed by flow cytometry. Regulatory T cell (Treg) function was analyzed by co-culturing effector CD4⁺T cells and Tregs collected from non-immunized mice.

Results: CII-immunized STS-2 KO mice developed arthritis more frequently than WT mice. Although the T cell activation profile and Th subset in spleen and LNs were similar between STS-2 KO and WT mice, STS-2 KO mice showed increased IL-2-producing CD4⁺T cells in spleen when compared with WT mice. Accordingly, STS-2 KO CD4⁺T cells promoted IL-2 production by TCR stimulation. However, STS-2 KO Tregs normally suppressed T cell proliferation.

Conclusion: We proved that STS-2 is involved in the arthritis development by collagen-induced arthritis. Higher IL-2 production from STS-2 KO T cells is suggested to have a main pathogenic role in arthritis development.

Keywords:

• Animal model
• collagen induced arthritis
• IL-2
• suppressor of TCR signaling-2
• rheumatoid arthritis

Conflict of interest

None.

Additional information

Funding

This work was supported by Grants-in-Aid from Japan Agency for Medical Research and Development [16ek041002h0001] and Japan Society for the Promotion of Science [24659274].