Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function.
CRACC is a self-associating member of the signaling lymphocytic activation molecule family that is expressed on cells of the immune system, including natural killer cells and activated T cells. Here we examine the function and mechanism of action of CRACC using several complementary approaches, including the generation of a CRACC-deficient mouse. Our results demonstrate that CRACC positively regulated natural killer cell functions by a mechanism dependent on the adaptor EAT-2 but not the related adaptor SAP. However, in the absence of EAT-2, CRACC potently inhibited natural killer cell function. CRACC was also inhibitory in T cells, which are typically devoid of EAT-2. Thus, CRACC can exert activating or inhibitory influences on cells of the immune system depending on cellular context and the availability of effector proteins.
Cruz-Munoz
Mario-Ernesto
ME
Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, Montréal, Québec, Canada H2W 1R7.
Dong
Zhongjun
Z
Shi
Xiaochu
X
Zhang
Shaohua
S
Veillette
André
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D020869:Gene Expression Profiling; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D011971:Receptors, Immunologic; C491225:Sh2d1b1 protein, mouse; D014157:Transcription Factors