A similar expression pattern Ruxolitinib was detected for CXCR3. The chemokine receptor for CXCL9-11 has a crucial role for recruitment of NK cells to sites of inflammation and accumulation in tumors 27, 28. Microarray data revealed that CXCR3 might also be suitable for distinguishing mouse NK-cell populations 29. In this study we evaluated the phenotype and function of CXCR3− and CXCR3+ NK cells for their suitability for comparisons with human NK-cell subsets with particular emphasis on the compartment-specific

distribution and coexpression of CXCR3 with CD27. Murine CXCR3− NK cells displayed higher CD16 and Ly49 receptor expression and stronger cytotoxicity than CXCR3+ NK cells, which proliferated stronger and Dabrafenib solubility dmso produced higher amounts of cytokines such as IFN-γ. Additionally, we found that CD27+ NK cells can be subdivided into CD27dimCXCR3−, CD27brightCXCR3− and CD27brightCXCR3+ populations and that both CD27 and CXCR3 expression changes upon stimulation of mouse NK cells. In conclusion, our data suggest that murine NK-cell subsets, complying in phenotype and function with those of humans, could be best identified by differential

expression of CXCR3 and CD27. The definition of functionally distinct NK-cell subsets in mice is useful for further in vivo analyses of NK-cell development, activation and migration with respect to their human counterparts. Murine NK cells lack CD56 expression, the major marker for discrimination Glycogen branching enzyme of functionally different NK-cell subsets in humans. CD56dim and CD56bright NK-cell

ratios vary between the compartments. If equivalent NK-cell subsets also exist in mice, one or more corresponding surface markers should be expressed at different levels when comparing the compartments. The surface receptor CD27 is discussed as a feasible marker for distinguishing murine NK-cell subsets and is also a current focus in human NK-cell research 25, 26. Microarray analyses of sorted human CD56dim and CD56bright NK cells also revealed a role for CXCR3, which is exclusively expressed on CD56bright NK cells 29. Therefore, we determined expression levels in different compartments in mice (Fig. 1). The expression patterns of CD27 and CXCR3 were relatively similar (Fig. 1A). The two markers were expressed in lower percentages on blood-derived and splenic NK cells as compared with NK cells from LN, BM and liver. Notably, exclusively lung-derived NK cells were not consistent in the ratio of CD27 and CXCR3 expression. The majority of NK cells from the lung expressed CD27 (65%), whereas only 10% of lung NK cells were CXCR3+. Further phenotypic analyses revealed that CXCR3 is predominantly expressed on CD16−/dim but not CD16bright NK cells (Fig. 1B). Remarkably, CXCR3 was almost exclusively expressed on CD27bright NK cells. This was consistent throughout all compartments (Fig. 1C). CD27− NK cells never expressed CXCR3 (Fig. 2).