title: Aryl hydrocarbon receptor is critical for homeostasis of invariant gammadelta T cells in the murine epidermis.
abstract: An immunoregulatory role of aryl hydrocarbon receptor (AhR) has been shown in conventional αβ and γδ T cells, but its function in skin γδ T cells (dendritic epidermal T cells [DETC]) is unknown. In this study, we demonstrate that DETC express AhR in wild-type 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 αβ T cells or conventional γδ 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 γδ 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 γδ T cells, and its consequences for the skin immune network.
authors.affiliation: Molecular Immunology, Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kadow
authors.forename: Bettina
authors.initials: B
authors.lastname: Jux
authors.forename: Sonja P
authors.initials: SP
authors.lastname: Zahner
authors.forename: Britta
authors.initials: B
authors.lastname: Wingerath
authors.forename: Stefanie
authors.initials: S
authors.lastname: Chmill
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.forename: Jan
authors.initials: J
authors.lastname: Hengstler
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse