Characterisation of NK cells and other cytotoxic killer cells in atopic dermatitis using single cell RNA sequencing

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The accumulation of multiple immune cell subtypes such as T cells, in particular Th2 cells, macrophages, and dendritic cells in lesional skin of patients with atopic dermatitis (AD) is known to have a sustaining role for the inflammation of the skin, while some cell types appear to have a regulatory function. Recently, a marked reduction of total peripheral blood natural killer (NK) cells along with a loss of mature CD56dim CD57+ NK cells and an enrichment of activated NK cell transcriptomic signatures in lesional skin has been observed in independent sets of patients with moderate to severe AD. Further, in a murine AD model, promotion of the survival and proliferation of NK cells reduced inflammation as well as the number of type 2 innate lymphoid cells (ILC2) and eosinophils. Based on these observations it has been speculated whether in AD, NK cells are recruited from the periphery to the inflamed skin as an endogenous counterregulatory response to type 2 skin inflammation, however, they could as well have inflammation promoting effects. So far, no in-depth and longitudinal NK cell phenotyping across tissues has been carried out in the context of AD. The proposed project aims at comprehensively defining NK cell heterogeneity at the single-cell level in both skin and blood of patients with AD, to examine NK cell effector functions, and to analyse the effects of type-2 blockade with the anti-IL4Rα antibody dupilumab and the anti-IL13 antibody tralokinumab.