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Skin-derived TSLP systemically expands regulatory T cells.

TitleSkin-derived TSLP systemically expands regulatory T cells.
Publication TypeJournal Article
Year of Publication2017
AuthorsLeichner, TM, Satake, A, Harrison, VSanoe, Tanaka, Y, Archambault, AS, Kim, BS, Siracusa, MC, Leonard, WJ, Naji, A, Wu, GF, Artis, D, Kambayashi, T
JournalJ Autoimmun
Date Published2017 May

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.

Alternate JournalJ. Autoimmun.
PubMed ID28126203
PubMed Central IDPMC5386815
Grant ListR01 HL107589 / HL / NHLBI NIH HHS / United States
R01 HL111501 / HL / NHLBI NIH HHS / United States
R01 NS083678 / NS / NINDS NIH HHS / United States