The junctional adhesion molecule JAML is a costimulatory receptor for epithelial gammadelta T cell activation.
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.
Witherden
Deborah A
DA
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Verdino
Petra
P
Rieder
Stephanie E
SE
Garijo
Olivia
O
Mills
Robyn E
RE
Teyton
Luc
L
Fischer
Wolfgang H
WH
Wilson
Ian A
IA
Havran
Wendy L
WL
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
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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