The role of SHP-2 on NK cell development and functions

Abstract

Abstract The SH2 domain-containing tyrosine phosphatase SHP-2 (PTPN11) has been shown to play essential roles in immune cell signaling. Several inhibitory receptors expressed on natural killer (NK) cells associate with SHP-2 to exert downstream functions. Here we examined the influence of SHP-2 on NK cell development and effector activity. Because SHP-2 is required for embryonic development in mice, we generated mice conditionally deficient for SHP-2 in NK cells. SHP-2fl/fl mice were crossed to NKp46-Cre mice in order to inactivate Ptpn11 in NKp46+ cells. These mice were also crossed to R26R-EYFP reporter mice to track cells with active Cre recombinase. We found an increase in NK cell frequency and number in these mice compared to littermate controls. The frequency of mature NK cells (CD11b+CD27−) was also increased in the periphery while decreased in the bone marrow. In addition, the homeostatic proliferation of SHP-2-deficient NK cells was impaired. However, effector functions were not affected significantly. These included IFN-γ production at the peak of the NK cell response during MCMV infection, rejection of β2-microglobulin deficient splenocytes, and degranulation via Ly49H using M157-transfected cells as targets. Taken together, our data suggest that SHP-2 is dispensable for NK cell effector functions and education, but is important for NK cell maturation.