340 Proteomic profiling of skin associated ILC and T cells reveals functional differences

Abstract

Innate lymphoid cells (ILC) are key players in tissue homeostasis and in the regulation of local immunity in barrier organs such as the skin. The functional properties of ILC are reflected by their protein expression, the proteins being the end-stage products of active genes. To characterize the proteome of human skin ILC, we performed in-depth proteomic analyses (mass spectrometry-based) on ILC2 and ILC3 purified from healthy skin (N=10), and their T cell counterparts (N=6). Skin derived ILC2 and ILC3 lacked the archetypical cytokine receptor signatures of ILC derived from other organs, but expressed the IL-18R, confirming previous observations in mice. Steady-state skin ILC showed constitutive expression of IL-14, IL-16, IL-36γ, IL-37 and TGF-β1. We determined the presence of proteins known as CD markers, transcription factors, immune checkpoints, homing and pathogen sensors in the ILC2 and ILC3 subsets, and found that multiple molecules were significantly differentially expressed in the two ILC types. For example, CD26, CD106, CD200R1, OX40L, CD280 were highly expressed in ILC2, whereas ILC3 showed high expression of CD11c, CD63, CD224, CD314, GITR and XCL1. In the differential expression analysis of skin ILC and skin T cells, we found that skin ILC showed higher expression of molecules involved in homeostasis, wound healing and tissue repair, such as FGA, VTN, HGF and BMP1. Conversely, in skin T cells, we also found significant differentially expressed proteins, including CD6. In conclusion, the proteomes of skin ILC reveal expression of previous unreported proteins and constitute an important resource for understanding ILC biology. Our data support the hypothesis that ILC protein expression differs among tissues.