Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function

Nat Immunol. 2009 Mar;10(3):297-305. doi: 10.1038/ni.1693. Epub 2009 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Gene Expression Profiling
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Receptors, Immunologic
  • Sh2d1b1 protein, mouse
  • Transcription Factors