TGF-β-Induced CD8+CD103+ Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells
نویسندگان
چکیده
Lupus nephritis is one of most severe complications of systemic erythematosus lupus and current approaches are not curative for lupus nephritis. Although CD4+Foxp3+ regulatory T cells (Treg) are crucial for prevention of autoimmunity, the therapeutic effect of these cells on lupus nephritis is not satisfactory. We previously reported that CD8+CD103+ Treg induced ex vivo with TGF-β1 and IL-2 (CD8+CD103+ iTreg), regardless of Foxp3 expression, displayed potent immunosuppressive effect on Th cell response and had therapeutic effect on Th cell-mediated colitis. Here, we tested whether CD8+CD103+ iTreg can ameliorate lupus nephritis and determined potential molecular mechanisms. Adoptive transfer of CD8+CD103+ iTreg but not control cells to chronic graft-versus-host disease with a typical lupus syndrome showed decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, lowered renal deposition of IgG/C3, and improved survival. CD8+CD103+ iTreg cells suppressed not only T helper cells but also B cell responses directly that may involve in both TGF-β and IL-10 signals. Using RNA-seq, we demonstrated CD8+CD103+ iTreg have its own unique expression profiles of transcription factors. Thus, current study has identified and extended the target cells of CD8+CD103+ iTreg and provided a possible application of this new iTreg subset on lupus nephritis and other autoimmune diseases.
منابع مشابه
TGF-β–dependent CD103 expression by CD8+ T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease
Destruction of the host intestinal epithelium by donor effector T cell populations is a hallmark of graft-versus-host disease (GVHD), but the underlying mechanisms remain obscure. We demonstrate that CD8(+) T cells expressing CD103, an integrin conferring specificity for the epithelial ligand E-cadherin, play a critical role in this process. A TCR transgenic GVHD model was used to demonstrate t...
متن کاملThe potential of human regulatory T cells generated ex vivo as a treatment for lupus and other chronic inflammatory diseases
Regulatory T cells prevent autoimmunity by suppressing the reactivity of potentially aggressive self-reactive T cells. Contact-dependent CD4+ CD25+ 'professional' suppressor cells and other cytokine-producing CD4+ and CD8+ T-cell subsets mediate this protective function. Evidence will be reviewed that T cells primed with transforming growth factor (TGF)-beta expand rapidly following restimulati...
متن کاملRegulatory T Cell Subtypes and TGF-β1 Gene Expression in Chronic Allograft Dysfunction
Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. Objectives: To eva...
متن کاملIn vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease.
CD103 (alphaEbeta7) has been shown to be an excellent marker for identifying in vivo-activated FoxP3(+)CD4(+) regulatory T (Treg) cells. It is unknown whether reinfusion of in vivo-activated donor-type CD103(+) Treg cells from recipient can ameliorate ongoing chronic graft-versus-host disease (GVHD). Here, we showed that, in a chronic GVHD model of DBA/2 (H-2(d)) donor to BALB/c (H-2(d)) recipi...
متن کاملInfluence of 1 Alpha, 25-Dihydroxyvitamin D3 on T Helper 17 Cells and Related Cytokines in Systemic Lupus Erythematosus
Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3...
متن کامل