@article{65199e85eb8a4b82bc363eaf2de2a3d9,
title = "SHP1 Phosphatase-Dependent T Cell Inhibition by CEACAM1 Adhesion Molecule Isoforms",
abstract = "T cell activation through the T cell receptor (TCR) is subsequently modified by secondary signals that are either stimulatory or inhibitory. We show that CEACAM1 adhesion molecule isoforms containing a long cytoplasmic domain inhibited multiple T cell functions as a consequence of TCR ligation. Overexpression of CEACAM1 resulted in decreased proliferation, allogeneic reactivity, and cytokine production in vitro and delayed type hypersensitivity and inflammatory bowel disease in mouse models in vivo. Conditioned deletion of CEACAM1 in T cells caused increased TCR-CD3 complex signaling. This T cell regulation was dependent upon the presence of immunoreceptor tyrosine-based inhibition motifs (ITIM) within the cytoplasmic domain of CEACAM1 and the Src homology 2 domain-containing protein tyrosine-phosphatase 1 (SHP1) in the T cell. Thus, CEACAM1 overexpression or deletion in T cells resulted in T cell inhibition or activation, respectively, revealing a role for CEACAM1 as a class of inhibitory receptors potentially amenable to therapeutic manipulation.",
keywords = "MOLIMMUNO, SIGNALING",
author = "Takashi Nagaishi and Lily Pao and Lin, {Sue Hwa} and Hideki Iijima and Arthur Kaser and Qiao, {Shuo Wang} and Zhangguo Chen and Jonathan Glickman and Najjar, {Sonia M.} and Atsushi Nakajima and Neel, {Benjamin G.} and Blumberg, {Richard S.}",
note = "Funding Information: We thank L.H. Glimcher, N. Iwakoshi, T. Tanaka, and M. Neurath for critical information on GFP-RV; J. Morrison, D. Bailey, and P. Gupta for their technical assistance; K. Holmes for the CC1 mAb; and R. Maurer for statistical analyses. T.N. was supported by Inflammatory Bowel Disease Young Investigator Award and Research Fellowship Award from the Crohn's & Colitis Foundation of America. L.P. was supported by an institutional NRSA T32CA81156. B.G.N. was supported by the National Institutes of Health (NIH) DK50693. R.S.B. was supported by NIH DK44319, DK51362, DK53056, and the Harvard Digestive Diseases Center (NIH DK34854). S.-H.L. was supported by NIH CA111479. S.M.N. was supported by grants from the NIH (DK54254), the American Diabetes Association, and the United States Department of Agriculture (USDA 205-38903-02315). R.S.B. is a scientific advisor to GenPat77, Berlin, Germany, which is developing therapeutics directed at CEACAM1. ",
year = "2006",
month = nov,
doi = "10.1016/j.immuni.2006.08.026",
language = "English (US)",
volume = "25",
pages = "769--781",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",
}