Aryl Hydrocarbon Receptor Is Critical for Homeostasis of Invariant γδ T Cells in the Murine Epidermis

An immunoregulatory role of aryl hydrocarbon receptor (AhR) has been shown in conventional alpha beta and gamma delta T cells, but its function in skin gamma delta T cells (dendritic epidermal T cells [DETC]) is unknown. In this study, we demonstrate that DETC express AhR in wildtype mice, and are specifically absent in the epidermis of AhR-deficient mice (AhR-KO). We show that DETC precursors are generated in the thymus and home to the skin. Proliferation of DETC in the skin was impaired in AhR-KO mice, resulting in a >90% loss compared with wild type. Surprisingly, DETC were not replaced by alpha beta T cells or conventional gamma delta T cells, suggesting a limited time frame for seeding this niche. We found that DETC from AhR-KO mice failed to express the receptor tyrosine kinase c-Kit, a known growth factor for gamma delta T cells in the gut. Moreover, we found that c-kit is a direct target of AhR, and propose that AhR-dependent c-Kit expression is potentially involved in DETC homeostasis. DETC are a major source of GM-CSF in the skin. Recently, we had shown that impaired Langerhans cell maturation in AhR-KO is related to low GM-CSF levels. Our findings suggest that the DETCs are necessary for LC maturation, and provide insights into a novel role for AhR in the maintenance of skin-specific gamma delta T cells, and its consequences for the skin immune network. The Journal of Immunology, 2011, 187: 3104-3110.