Block of both TGF-β and IL-2 signaling impedes Neurophilin-1+ regulatory T cell and follicular regulatory T cell development

Liang Li, Shu Han Yang, Yuan Yao, Yu Qing Xie, Yan Qing Yang, Yin Hu Wang, Xue Ying Yin, Hong Di Ma, M. Eric Gershwin, Zhe Xiong Lian

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra-/- (abbreviated as Il2ra-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra-/-Tg mice contained Neuropilin-1+ or PD-1hi phenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-β and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells.

Original languageEnglish (US)
Pages (from-to)e2439
JournalCell death & disease
Volume7
Issue number10
DOIs
StatePublished - Oct 27 2016

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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