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

<p><b>Objectives:</b> 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.</p> <p><b>Methods:</b> 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.</p> <p><b>Results:</b> 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.</p> <p><b>Conclusion:</b> 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.</p

Additional file 1: Supplement 1. of A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production

Correlations of the plasma concentration of IL-12p40 with those of IL-12p70 and IL-23. a The plasma concentration of IL-12p40 was correlated with that of IL-12p70 (rho = 0.33, p = 0.027). b There were no correlation between the plasma concentrations of IL-12p40 and IL-23. Supplement 2. Correlation between the proportion of CXCR3+ cells among CD3+CD4+ cells and the dose of glucocorticoids. The proportion of CXCR3+ cells among CD3+CD4+ cells was negatively correlated with the dose of glucocorticoids (rho = − 0.63 and p < 0.01). Statistical analysis was performed using Spearman’s rank correlation coefficient. (DOCX 34 kb

Additional file 1 of Management and treatment outcomes of rheumatoid arthritis in the era of biologic and targeted synthetic therapies: evaluation of 10-year data from the KURAMA cohort

Additional file 1: S. Table1. Baseline characteristics of patients with RA who enrolled in the annual RA survey

Affected rate of joint symptoms.

<p>Affected rate of joint symptoms. Each joint is arranged in the order of right and left. S:shoulder, E:elbow, W:wrist, K:knee.</p

Summary of the KURAMA database.

*<p>Stage and Class represent Steinbrocker's stage and class, respectively.</p><p>SD: standard deviation.</p

Six subgroups of evaluations of the 28 joints in RA.

<p>Results of clustering analysis with Ward method using randomly obtained 5,383 evaluations of the 28 joints in 1,314 patients were plotted.</p

Time course of urine protein, OPN full and OPN N-half concentration in three patients with LN treated with immunosuppressive therapy.

<p>There were three patients with LN from whom we could obtain serial samples before and after treatment. On Day 0, prednisolone (1 mg/kg/day) was started.</p

Relationship of the 28-joint involvement.

<p>The 1^st and 2^nd components of eigen vectors of the joint symptoms are plotted, using principal component analysis of the 28 joint involvement for tenderness (A) and swelling (C) or using that of the 20 joint involvement other than large and wrist joints for tenderness (B) and swelling (D). The results are representatives of five analyses based on resampled assessments. Green: large and wrist joints. Red: MCP joints. Blue: PIP joints.</p

Correlation of OPN N-half level with thrombin or MMP-3 activity in urine.

<p>Correlation of urine OPN N-half level with urine thrombin activity (A) or urine MMP-3 activity (B) in SLE patients (N = 56). Values were corrected by calculating the ratio to urine Cre concentration. r²: coefficient of determination of a linear regression analysis.</p

Correlation of urine OPN N-half with renal damage markers.

<p>Correlation of urine OPN N-half with renal damage markers.</p