title: Direct control of regulatory T cells by keratinocytes.
abstract: Environmental challenges to epithelial cells trigger gene expression changes that elicit context-appropriate immune responses. We found that the chromatin remodeler Mi-2β controls epidermal homeostasis by regulating the genes involved in keratinocyte and immune-cell activation to maintain an inactive state. Mi-2β depletion resulted in rapid deployment of both a pro-inflammatory and an immunosuppressive response in the skin. A key target of Mi-2β in keratinocytes is the pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP). Loss of TSLP receptor (TSLPR) signaling specifically in regulatory T (Treg) cells prevented their activation and permitted rapid progression from a skin pro-inflammatory response to a lethal systemic condition. Thus, in addition to their well-characterized role in pro-inflammatory responses, keratinocytes also directly support immune-suppressive responses that are critical for re-establishing organismal homeostasis.
authors.affiliation: Cuteneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kashiwagi
authors.affiliation: Cuteneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hosoi
authors.affiliation: Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
authors.forename: Jen-Feng
authors.initials: JF
authors.lastname: Lai
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Brissette
authors.affiliation: Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.affiliation: Cuteneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Morgan
authors.affiliation: Cuteneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Katia
authors.initials: K
authors.lastname: Georgopoulos
mesh_terms: D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics; D015603:Keratinocytes / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; C509277:Mi-2beta protein, mouse; D004265:DNA Helicases; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse