Skin-derived TSLP systemically expands regulatory T cells

Theresa M. Leichner, Atsushi Satake, Victor Sanoe Harrison, Yukinori Tanaka, Angela S. Archambault, Brian S. Kim, Mark C. Siracusa, Warren J. Leonard, Ali Naji, Gregory F. Wu, David Artis, Taku Kambayashi

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Regulatory T cells (Tregs) are a subset of CD4+ T cells with suppressive function and are critical for limiting inappropriate activation of T cells. Hence, the expansion of Tregs is an attractive strategy for the treatment of autoimmune diseases. Here, we demonstrate that the skin possesses the remarkable capacity to systemically expand Treg numbers by producing thymic stromal lymphopoietin (TSLP) in response to vitamin D receptor stimulation. An ∼2-fold increase in the proportion and absolute number of Tregs was observed in mice treated topically but not systemically with the Vitamin D3 analog MC903. This expansion of Tregs was dependent on TSLP receptor signaling but not on VDR signaling in hematopoietic cells. However, TSLP receptor expression by Tregs was not required for their proliferation. Rather, skin-derived TSLP promoted Treg expansion through dendritic cells. Importantly, treatment of skin with MC903 significantly lowered the incidence of autoimmune diabetes in non-obese diabetic mice and attenuated disease score in experimental autoimmune encephalomyelitis. Together, these data demonstrate that the skin has the remarkable potential to control systemic immune responses and that Vitamin D-mediated stimulation of skin could serve as a novel strategy to therapeutically modulate the systemic immune system for the treatment of autoimmunity.

本文言語English
ページ(範囲)39-52
ページ数14
ジャーナルJournal of Autoimmunity
79
DOI
出版ステータスPublished - 2017 5 1
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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