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Updated: Feb 21, 2026
Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice
Namiko Okabe1, Koichiro Ohmura1, Masaki Katayama2
1a Department of Rheumatology and Clinical Immunology , Graduate School of Medicine, Kyoto University , Kyoto , Japan.
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.
Insights
Suppressor of TCR signaling-2 (STS-2) deficiency exacerbates autoimmune arthritis in mice. Increased IL-2 production by T cells in STS-2 KO mice is implicated in disease development, highlighting STS-2
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Genome-wide association studies (GWAS) identified Suppressor of TCR signaling-2 (STS-2) as a susceptibility gene for rheumatoid arthritis (RA).
- The precise role of STS-2 in the pathogenesis of autoimmune arthritis remains to be fully elucidated.
Purpose of the Study:
- To investigate the involvement of STS-2 in the development of autoimmune arthritis using a collagen-induced arthritis (CIA) mouse model.
- To determine the impact of STS-2 deficiency on T cell responses and regulatory T cell (Treg) function in the context of arthritis.
Main Methods:
- Comparison of arthritis incidence between STS-2 knock-out (KO) and wild-type (WT) mice following immunization with chicken type II collagen (CII).
- Flow cytometry analysis of CD4+ helper T cell (Th) subsets and intracellular cytokine production in splenocytes and lymph node cells.
- Assessment of Treg suppressive function through co-culture experiments with effector T cells.
Main Results:
- STS-2 KO mice exhibited a higher frequency of arthritis development compared to WT mice after CII immunization.
- While overall T cell activation profiles and Th subsets were similar, STS-2 KO mice showed significantly increased IL-2 production from CD4+ T cells in the spleen.
- STS-2 deficiency enhanced IL-2 production by T cells upon TCR stimulation, whereas Treg function remained unaffected.
Conclusions:
- STS-2 plays a crucial role in regulating the development of collagen-induced autoimmune arthritis.
- Elevated IL-2 production by STS-2 deficient T cells is identified as a key pathogenic mechanism contributing to arthritis development.
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