Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 16 November 2007:
Vol. 318. no. 5853, pp. 1141 - 1143
DOI: 10.1126/science.1148536
Prev | Table of Contents | Next

Reports

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

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.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Galectin-9 Is a High Affinity IgE-binding Lectin with Anti-allergic Effect by Blocking IgE-Antigen Complex Formation.
T. Niki, S. Tsutsui, S. Hirose, S. Aradono, Y. Sugimoto, K. Takeshita, N. Nishi, and M. Hirashima (2009)
J. Biol. Chem. 284, 32344-32352
   Abstract »    Full Text »    PDF »
Human Pregnancy Up-Regulates Tim-3 in Innate Immune Cells for Systemic Immunity.
J. Zhao, Z. Lei, Y. Liu, B. Li, L. Zhang, H. Fang, C. Song, X. Wang, G.-M. Zhang, Z.-H. Feng, et al. (2009)
J. Immunol. 182, 6618-6624
   Abstract »    Full Text »    PDF »
Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation.
M. Nakayama, H. Akiba, K. Takeda, Y. Kojima, M. Hashiguchi, M. Azuma, H. Yagita, and K. Okumura (2009)
Blood 113, 3821-3830
   Abstract »    Full Text »    PDF »
Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells.
J. Klibi, T. Niki, A. Riedel, C. Pioche-Durieu, S. Souquere, E. Rubinstein, S. Le Moulec, J. Guigay, M. Hirashima, F. Guemira, et al. (2009)
Blood 113, 1957-1966
   Abstract »    Full Text »    PDF »
Galectin-9 Increases Tim-3+ Dendritic Cells and CD8+ T Cells and Enhances Antitumor Immunity via Galectin-9-Tim-3 Interactions.
K. Nagahara, T. Arikawa, S. Oomizu, K. Kontani, A. Nobumoto, H. Tateno, K. Watanabe, T. Niki, S. Katoh, M. Miyake, et al. (2008)
J. Immunol. 181, 7660-7669
   Abstract »    Full Text »    PDF »
Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection.
R. B. Jones, L. C. Ndhlovu, J. D. Barbour, P. M. Sheth, A. R. Jha, B. R. Long, J. C. Wong, M. Satkunarajah, M. Schweneker, J. M. Chapman, et al. (2008)
J. Exp. Med. 205, 2763-2779
   Abstract »    Full Text »    PDF »
TIMs: central regulators of immune responses.
D. A. Hafler and V. Kuchroo (2008)
J. Exp. Med. 205, 2699-2701
   Abstract »    Full Text »    PDF »
Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices.
A. Nobumoto, K. Nagahara, S. Oomizu, S. Katoh, N. Nishi, K. Takeshita, T. Niki, A. Tominaga, A. Yamauchi, and M. Hirashima (2008)
Glycobiology 18, 735-744
   Abstract »    Full Text »    PDF »
Lack of TIM-3 Immunoregulation in Multiple Sclerosis.
L. Yang, D. E. Anderson, J. Kuchroo, and D. A. Hafler (2008)
J. Immunol. 180, 4409-4414
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)