Therapeutic potential of TGF-β-induced CD4(+) Foxp3(+) regulatory T cells in autoimmune diseases

Autoimmunity. 2011 Feb;44(1):43-50. doi: 10.3109/08916931003782163. Epub 2010 Jul 29.

Abstract

Foxp3(+) T regulatory cell (Treg) subsets play a crucial role in the maintenance of immune homeostasis against self-antigens. The lack or dysfunction of these cells contributes to the pathogenesis and development of many autoimmune diseases. Therefore, manipulation of these cells may provide a novel therapeutic approach to treat autoimmune diseases. In this review, we provide current opinions concerning the classification, developmental, and functional characterization of Treg subsets. Particular emphasis will be focused on the therapeutic role of TGF-β-induced CD4M(+) Foxp3(+) cells (iTregs) in established autoimmune disease. Moreover, the similarity and diversity of iTregs and naturally occurring, thymus-derived CD4(+) CD25(+) Foxp3(+) regulatory T cells (nTregs) will be discussed, including the finding that the pro-inflammatory cytokine IL-6 can convert nTregs to IL-17-producing cells, whereas iTregs induced by TGF-β are resistant to the effects of this cytokine. Understanding these aspects may help to determine how Tregs can be used in the treatment of autoimmune diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy*
  • CD4-Positive T-Lymphocytes*
  • Forkhead Transcription Factors / analysis
  • Humans
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Self Tolerance
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukin-6
  • Transforming Growth Factor beta