AhR-mediated activation of innate lymphocytes restrains tissue-resident memory-like CD8+ T cell responses during contact hypersensitivity

Allergic contact dermatitis (ACD) and the mouse model of hapten-induced contact hypersensitivity (CHS) are inflammatory skin responses triggered by the repeated exposure to exogenous allergens and haptens. ACD and CHS effector responses have been extensively studied, but the regulatory mechanisms that control inflammation and determine the kinetics of its resolution are still incompletely understood. In addition, although CHS can be mediated by both innate and adaptive effector cells in a non-redundant manner, leading to distinct skin pathologies, their interplay during the course of inflammation remains so far unaddressed. Here, we show that NKp46+ innate lymphoid cells (ILCs) limit the extent of CHS inflammation by modulating the CD8+ TRM immune compartment. This regulatory effect of ILCs depends on the expression of the ligand-induced transcription factor aryl-hydrocarbon receptor (AhR). AhR-deficiency in NKp46+ ILCs did not affect the memory response to hapten, but led to spatial propagation and amplification of inflammatory response in the skin. This phenotype correlated with increased numbers of Ifng-producing CD8+ TRM-like cells and neutrophilic infiltration in the skin. Our study thereby demonstrates a novel AhR-driven innate-adaptive immune interplay in regulating skin inflammation.