Skin resident CD4- CD8- (double-negative) αβT cells produce IL-17A during Nannizzia gypsea dermatophytic infection

Congreso; Reunión Anual de Sociedades de Biociencias. LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica. LXX Reunión Anual de la Sociedad de Argentina de Inmunología. 3rd French-Argentine Immunology Congress. Reunión Anual 2022 de la Sociedad Ar; 2022

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