Format

Send to:

Choose Destination
See comment in PubMed Commons below
Eur J Immunol. 2013 Sep;43(9):2473-83. doi: 10.1002/eji.201242676. Epub 2013 Jun 18.

CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling.

Author information

  • 1Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on activated natural killer (NK) cells wherein it inhibits lysis of CEACAM1-bearing tumor cell lines. The mechanism for this is unknown. Here, we show that interleukin-2-induced expression of CEACAM1 on both mouse and primary human NK cells impairs the ability of NK gene complex group 2 member D (NKG2D) to stimulate cytolysis of CEACAM1-bearing cells. This process requires the expression of CEACAM1 on the NK cells and on the tumor cells, which is consistent with the involvement of trans-homophilic interactions between CEACAM1. Mechanistically, co-engagement of NKG2D and CEACAM1 results in a biochemical association between these two surface receptors and the recruitment of Src homology phosphatase 1 by CEACAM1 that leads to dephosphorylation of the guanine nucleotide exchange factor Vav1 and blockade of downstream signaling that is associated with the initiation of cytolysis. Thus, CEACAM1 on activated NK cells functions as an inhibitory receptor for NKG2D-mediated cytolysis, which has important implications for understanding the means by which CEACAM1 expression adversely affects tumor immunity.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

CEACAM1; Cytolysis; Interleukin-2; NK cell; NKG2D

PMID:
23696226
[PubMed - indexed for MEDLINE]
PMCID:
PMC3775953
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for John Wiley & Sons, Inc. Icon for PubMed Central
    Loading ...
    Write to the Help Desk