title: The junctional adhesion molecule JAML is a costimulatory receptor for epithelial gammadelta T cell activation.
abstract: Gammadelta T cells present in epithelial tissues provide a crucial first line of defense against environmental insults, including infection, trauma, and malignancy, yet the molecular events surrounding their activation remain poorly defined. Here we identify an epithelial gammadelta T cell-specific costimulatory molecule, junctional adhesion molecule-like protein (JAML). Binding of JAML to its ligand Coxsackie and adenovirus receptor (CAR) provides costimulation leading to cellular proliferation and cytokine and growth factor production. Inhibition of JAML costimulation leads to diminished gammadelta T cell activation and delayed wound closure akin to that seen in the absence of gammadelta T cells. Our results identify JAML as a crucial component of epithelial gammadelta T cell biology and have broader implications for CAR and JAML in tissue homeostasis and repair.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Witherden
authors.forename: Petra
authors.initials: P
authors.lastname: Verdino
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Rieder
authors.forename: Olivia
authors.initials: O
authors.lastname: Garijo
authors.forename: Robyn E
authors.initials: RE
authors.lastname: Mills
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Fischer
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Havran
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000293:injuries; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014945:Wound Healing
chemical_list: C568772:CLMP protein, mouse; D015815:Cell Adhesion Molecules; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011991:Receptors, Virus; D019869:Phosphatidylinositol 3-Kinases
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