Troy binding to lymphotoxin-α activates NFκB mediated transcription

Abstract

Troy is a TNFR superfamily member that is highly expressed in developing hair follicles. Its possible function and ligand in skin have, however, been unknown. Here we demonstrate that an immunomodulatory cytokine, lymphotoxin-α (LTα), is a functional ligand of Troy by 3 biochemical approaches: (1) Immunoprecipitation assays revealed that LTα, but not LTβ or any obligate combination of LTα and LTβ, binds to Troy. (2) Co-transfection of LTα with Troy sharply upregulated NFκB reporter transcription, whereas LTβ or a combination of LTα and LTβ did not. (3) Recombinant LTα protein upregulated NFκB activity through Troy in a dosedependent manner. We further found that LTα is expressed in dermal papillae of developing hair follicles, whereas Troy was expressed in adjacent matrix region. This suggested involvement of LTα-Troy signaling in mesenchyme-epithelium interactions during hair follicle development.However, in Troy mutant mice that we generated, hair subtype composition and morphology were altered slightly if at all. The present study thus suggested a subtle function of the newly identifiedLTα-Troy pathway in skin appendage development, however, it may have an additional action compensated by a parallel EDA signaling pathway.