1010 IL-15 as a regulator of human skin macrophages and iNKT cells ex vivo and novel therapeutic target in IFNγ-driven inflammatory dermatoses

Interleukin (IL)-15 is a pleiotropic immunomodulatory and anti-apoptotic cytokine. It stimulates the proliferation survival of key immunocytes including macrophages (MACs) invariant natural killer T (iNKT) cells, which are immunoinhibitory via IL-10 release clinically relevant in interferon gamma (IFNγ)-mediated inflammatory skin diseases such as alopecia areata. Using immunofluorescence microscopy, we have asked this pilot study how recombinant human (rh) IL-15 impacts MHC class II+ CD68+/CD206+/IL-10+ MACs, iNKT10+ cells intact ex vivo under IFNγ-induced conditions. 4-mm punch biopsies healthy full-thickness were organ-cultured treated with 100ng/mL rhIL-15 presence or absence 100 IU/mL IFNγ for six days. Quantitative immunohistomorphometry showed that significantly reduced number (i.e., dermal MACs dendrocytes), thereby inhibiting antigen presentation compared to only IFNγ. Moreover, protected even restored CD206+MACs iNKT producing/secreting To investigate if these effects mediated activation private receptor, successfully silenced IL-15Rα vivo. This downregulated well CD206+IL-10+MACs, but increased CD68+MACs siIL-15Rα. These data suggest IL-15/IL-15Rα signaling important maintenance function iNKT10+cells when excess present. Thus, agonists may exert therapeutic benefit role IFNγ, areata, psoriasis, vitiligo, lichen planus.