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Significance The cross-talk between the microbiota and the immune system plays a fundamental role in the control of host physiology. However, the tissue-specific factors controlling this dialogue remain poorly understood. Here we demonstrate that T cell responses to commensal colonization are associated with the development of organized cellular clusters within the skin epithelium. Keratinocyte-intrinsic MHC class II expression was required for the selective accumulation of commensal-induced IFN-γ–producing CD4+ T cells within the skin. This work uncovers an unexpected role for MHC class II expression by keratinocytes in the control of homeostatic type 1 responses to the microbiota. Our findings have important implications for the understanding of the tissue-specific rules governing the dialogue between a host and its microbiota.

Keratinocyte-intrinsic MHCII expression controls microbiota-induced Th1 cell responses