Keratinocyte-intrinisic MHCII expression controls Microbiota-specific Th1 cell responses

The crosstalk 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 clusters within the skin epithelium. These organized lymphocyte clusters are surrounded by specialized keratinocytes expressing a discrete program associated with antigen presentation and anti-microbial defense. Notably, IL-22-mediated keratinocyte-intrinsic MHC class II expression was required for the selective accumulation of commensal-induced IFN-?? but not IL-17A-producing CD4+ T cells within the skin. Together, this work uncovers an unexpected role for keratinocyte-mediated antigen presentation in the licensing of homeostatic type 1 responses to the microbiota, findings that have important implications in our understanding of the unique rules governing the dialogue between the host and its microbiota. Overall design: Keratinocytes were FACsorted from the epidermis of ear pinnae of C57BL/6 mice from naïve mice or day 14 post topical association with S. epidermidis NIHLM087. CD49f+Sca-1+ Keratinocytes were sorted as CD45-CD31-CD34- cells and further separated based on their expression of MHCII.