Though these drugs tend to be effective alopecia areata (AA) therapeutics, AA quickly relapses after discontinuing treatment with JAK1/3 inhibitors (JAKi). One reason could be that JAKi also block the signaling of AA-protective cytokines that signal via the common γ-chain, which is also used by interleukin-15 (IL-15). IL-15 is known to suppress mouse HF apoptosis, promote murine HF growth in vivo, and is required to maintain (AA-protective!) iNKT cells. Moreover, it is unclear how IL-15 affects human hair follicle (HF)-immune privilege (IP) and catagen development, namely via signaling through its private receptor, IL-15Rα. To clarify this, organ-cultured, healthy human anagen scalp HFs were treated with rhIL-15 before or after IFNγ-induced HF-IP collapse. This showed that IL-15 protects from HF-IP collapse, restores HF-IP (assessed by MHC class Ia, MICA, and α-MSH quantitative immunohistomorphometry), and retards catagen development. Instead, IL-15Rα silencing ex vivo induces premature catagen, inhibits hair matrix proliferation and weakens the HF-IP (=increased expression of MHCIa/β2-mg; decreased production of the HF IP guardians, α-MSH and TGFβ2). Moreover, lesional skin of AA patients showed significantly reduced protein expression of both, IL-15Rα and the common γ-chain, not only in lesional but already in non-lesional AA HFs, indicating reduced sensitivity to IL-15 signaling in AA patients. Thus, contrary to often reverberated misconceptions, IL-15 also promotes human hair growth and acts as a human HF IP guardian (but might simultaneously promote selected AA-related immune responses). Thus, selectively stimulating intrafollicular IL-15Rα signaling could effectively promote hair (re-)growth and prevent rapid AA relapse after discontinuation of JAKi therapy.

ESDR013 - IL-15/IL-15Rα signaling is a guardian of human hair follicle immune privilege and promotes hair growth

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.