Abstract
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.
Highlights
Systemic lupus erythematosus (SLE) is a serious autoimmune disease with incompletely understood pathogenesis
We previously reported that CD8+CD103+ induced Treg cells (iTreg) induced ex vivo with TGF-β and IL-2 potently suppressed Th cell response and Th1/Th17-mediated colitis, regardless of Foxp3 expression [20]
CD8+CD103− cells were sorted from CD8 Med as CD8 control cells (CD8 Med), CD8+CD103+ cells were sorted from iTreg cells as CD8+CD103+ iTreg cells as previously described [20]
Summary
Systemic lupus erythematosus (SLE) is a serious autoimmune disease with incompletely understood pathogenesis. A foremost cause of morbidity and mortality, is present in up to 60% SLE patients [2], and features immune complex deposition in the glomerulus, causing tissue damage and proteinuria. B cell depletion using rituximab has been used for the treatment of SLE and many autoimmune and chronic inflammatory diseases [4, 5], but its role is restricted for incapable of depleting long-lived plasma cells [6]. All of these treatment options are not a permanent cure which would be one that ideally reverses immune imbalance
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