αβT cells produce IL-17A during Nannizzia gypsea dermatophytic infection.

BECCACECE I; BURSTEIN VL; ALMEIDA M; GUASCONI L; MENA C; CHIAPELLO LS

Congreso; Reunión conjunta SAIC, SAI & FAIC SAFIS 2022; 2022

Dermatophytosis is a highly prevalent superficial fungal diseasethat affects keratinized tissues such as the skin, hair and nails. Wehave previously reported that IL-17A produced by skin resident γδTand αβT cells is important in the defense against dermatophytes.Furthermore, the single depletion of γδT cells does not lead to increasedsusceptibility since IL-17A production by epidermal cells isnot abolished. In this study we aim to further characterize the phenotype,origin, and function of the βTCR+ IL-17A-producing cells in theskin. IL-17A-GFP-reporter and CD8 KO mice were epicutaneouslyinfected with Nannizzia gypsea in the back. To study resident T cells,a daily dose of Fingolimod (FTY-720, 2μg/g) was intraperitoneallyinjected starting 24 h prior to infection. On day 6 post-infection, backskin was removed and treated with Trypsin/EDTA (2 h/37°C) andepidermal cell suspensions were used for FACS analysis and fungalburden determination. At 6 days post-infection, FACS analysis revealedthat IL-17A+ βTCR+ cells were mostly made up of CD4-CD8-double-negative (DN) cells. This DN population was not affectedby FTY-720 treatment suggesting that this subset is maintained inthe skin independently of the influx of T lymphocytes from draininglymph nodes. Previous reports have shown that DN T cells can havea thymic origin or derive from peripheral CD8 T cells by down-regulationof the CD8 receptor. After N. gypsea infection, CD8 KO miceexhibited a decreased IL-17A production by skin T cells (P= 0.0358)when compared to WT infected mice. However, DN cells were stillpresent suggesting that they do not arise from CD8 T cells duringdermatophytosis. Taken together, these data show that skin residentIL-17A-producing βTCR+ T cells are mostly double-negative for CD4and CD8 expression. Despite the increased susceptibility of CD8KO mice to infection, these DN cells do not derive from CD8 T cellsso further studies are needed to determine their origin and function.