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. 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.