CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling
| Autor: | Hosomi, Shuhei, Chen, Zhangguo, Baker, Kristi, Chen, Lanfen, Huang, Yu-Hwa, Olszak, Torsten, Zeissig, Sebastian, Wang, Jing H, Mandelboim, Ofer, Beauchemin, Nicole, Lanier, Lewis L, Blumberg, Richard S |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Knockout
Immunology Apoptosis Inbred C57BL Small Interfering Article Cell Line NKG2D Non-Receptor Type 6 Mice Cell Line Tumor Killer Cells Animals Humans NK cell Phosphorylation RNA Small Interfering Proto-Oncogene Proteins c-vav CEACAM1 Mice Knockout Tumor Cytolysis Protein Tyrosine Phosphatase Non-Receptor Type 6 Carcinoembryonic Antigen Killer Cells Natural Mice Inbred C57BL NK Cell Lectin-Like Receptor Subfamily K Natural RNA Interleukin-2 RNA Interference Protein Tyrosine Phosphatase Signal Transduction |
| Zdroj: | Hosomi, S; Chen, Z; Baker, K; Chen, L; Huang, YH; Olszak, T; et al.(2013). CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. European Journal of Immunology, 43(9), 2473-2483. doi: 10.1002/eji.201242676. UCSF: Retrieved from: http://www.escholarship.org/uc/item/66x4c1md European journal of immunology, vol 43, iss 9 |
| DOI: | 10.1002/eji.201242676. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|