TGF-β-induced CD8+CD103+ regulatory T cells show potent therapeutic effect on chronic graft-versus-host disease lupus by suppressing B cells

Haowen Zhong, Ya Liu, Zhenjian Xu, Peifeng Liang, Hui Yang, Xiao Zhang, Jun Zhao, Junzhen Chen, Sha Fu, Ying Tang, Jun Lv, Julie Wang, Nancy Olsen, Anping Xu, Song Guo Zheng

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Article number35
JournalFrontiers in immunology
Volume9
Issue numberJAN
DOIs
StatePublished - Jan 30 2018

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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