Specific Regulation of T Helper Cell 1-mediated Murine Colitis by CEACAM1

Speaker: 方宜婷                            Date: 05/12/2004 13:00~14:00

Commentator: 黎煥耀      老師                  Room: 602

Abstract:

      Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1), a member of the carcinoembryonic antigen family of glycoproteins, is expressed in a variety of cell types, including epithelial cell, endothelial cell, and hematopoietic cell lineages. The major proven functions of CEACAM1 are intercellular adhesion and as bacterial or viral receptors. These interactions with CEACAM1 are likely linked to cell signaling leading to regulation of cell growth and differentiation. In previous studies, ligation of CEACAM1 with CEACAM1-specific mAbs or bacterial products either significantly suppressed or activated T cells in vitro, but the explanation for the different effects remains unknown (1,2). In addition, there is no available evidence in vivo to support a role for CEACAM1 in regulating T cell-mediated inflammatory processes. In this paper, the authors showed that anti-CEACAM1 mAb (CC1) protected mice from TNBS and oxazolone colitis when administered before the effector phase. The suppression of colitis was associated with a specific reduction in Th1 cytokine production (IFN-g) but not Th2 cytokine (IL-4). Ligation of CEACAM1 by the CC1 mAb suppressed T-bet activation, while STAT4 activation was unaffected. These results demonstrate a the major functional effect of CEACAM1 in vivo on the downregulation of the Th1-mediated inflammation in two colitis models. Furthermore, ligation of CEACAM1 on T cells with the murine hepatitis virus spike protein specifically inhibited the differentiation and activation of Th1 cells in vitro. These studies point toward an important role for CEACAM1 in regulating Th1-mediated inflammatory disease such as inflammatory bowel disease or virus-mediated immunopathology (3).

References:

1.     Boulton, I.C., and Gray-Owen, S.D. Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4⁺ T lymphocytes. Nat. Immunol. 3:229-236, 2002.

2.     Donda, A. et al. Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response. Eur. J. Immunol. 30:2593-2603, 2000.

3.     Iijima, H. et al. Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J. Exp. Med. 199:471-482, 2004.