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Science 318 (5853): 1141-1143

Copyright © 2007 by the American Association for the Advancement of Science

Promotion of Tissue Inflammation by the Immune Receptor Tim-3 Expressed on Innate Immune Cells

Ana C. Anderson,1* David E. Anderson,1* Lisa Bregoli,1* William D. Hastings,1 Nasim Kassam,1 Charles Lei,1 Rucha Chandwaskar,1 Jozsef Karman,1 Ee W. Su,2 Mitsuomi Hirashima,3 Jeffrey N. Bruce,4 Lawrence P. Kane,2 Vijay K. Kuchroo,1{dagger} David A. Hafler1

Abstract: CD4+ T helper 1 (TH1) cells are important mediators of inflammation and are regulated by numerous pathways, including the negative immune receptor Tim-3. We found that Tim-3 is constitutively expressed on cells of the innate immune system in both mice and humans, and that it can synergize with Toll-like receptors. Moreover, an antibody agonist of Tim-3 acted as an adjuvant during induced immune responses, and Tim-3 ligation induced distinct signaling events in T cells and dendritic cells; the latter finding could explain the apparent divergent functions of Tim-3 in these cell types. Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions.

1 Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
2 Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
3 Immunology and Immunopathology, School of Medicine, Kagawa University, Takamatsu, Japan.
4 Gabriele Bartoli Brain Tumor Research Laboratory, Department of Neurological Surgery, Neurological Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: vkuchroo{at}rics.bwh.harvard.edu (V.K.K.)

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