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Science 329 (5996): 1205-1210

Copyright © 2010 by the American Association for the Advancement of Science

The Junctional Adhesion Molecule JAML Is a Costimulatory Receptor for Epithelial {gamma}{delta} T Cell Activation

Deborah A. Witherden,1 Petra Verdino,2 Stephanie E. Rieder,1,* Olivia Garijo,1 Robyn E. Mills,1,{dagger} Luc Teyton,1 Wolfgang H. Fischer,4 Ian A. Wilson,2,3 Wendy L. Havran1,{ddagger}

Abstract: {gamma}{delta} 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 {gamma}{delta} 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 {gamma}{delta} T cell activation and delayed wound closure akin to that seen in the absence of {gamma}{delta} T cells. Our results identify JAML as a crucial component of epithelial {gamma}{delta} T cell biology and have broader implications for CAR and JAML in tissue homeostasis and repair.

1 Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
2 Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3 The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
4 Peptide Biology, The Salk Institute, La Jolla, CA 92037, USA.

* Present address: Abbott Bioresearch Center, Worcester, MA 01605, USA

{dagger} Present address: University of California, San Francisco, San Francisco, CA 94143, USA

{ddagger} To whom correspondence should be addressed. E-mail: havran{at}scripps.edu.

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