Blockade of IL-7 signaling suppresses inflammatory responses and reverses alopecia areata in C3H/HeJ mice

  • Sci Adv. 2021 Apr 2;7(14):eabd1866. doi: 10.1126/sciadv.abd1866.
Zhenpeng Dai  1 ,  Eddy Hsi Chun Wang  1 ,  Lynn Petukhova  1 ,  Yuqian Chang  1 ,  Eunice Yoojin Lee  1 ,  Angela M Christiano  2  3
Affiliations
  • 1. Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
  • 2. Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. [email protected].
  • 3. Department of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
PMID: 33811067 DOI: 10.1126/sciadv.abd1866
Abstract

The interleukin-7 (IL-7) signaling pathway plays an important role in regulation of T cell function and survival. We detected overexpression of IL-7 in lesional skin from both humans and C3H/HeJ mice with alopecia areata (AA), a T cell-mediated Autoimmune Disease of the hair follicle. We found that exogenous IL-7 accelerated the onset of AA by augmenting the expansion of alopecic T cells. Conversely, blockade of IL-7 stopped the progression of AA and reversed early AA in C3H/HeJ mice. Mechanistically, we observed that IL-7Rα blockade substantially reduced the total number of most T cell subsets, but relative sparing of regulatory T cells (Tregs). We postulated that short-term anti-IL-7Rα treatment in combination with a low dose of Treg-tropic cytokines might improve therapeutic efficacy in AA. We demonstrated that short-term IL-7Rα blockade in combination with low doses of Treg-tropic cytokines enhanced therapeutic effects in the treatment of AA, and invite further clinical investigation.

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