NK cells in TAP2-deficient patients Functional aberrant expression of CCR2 receptor on chronically activated

Abstract Chemokines play a pivotal role in homeostatic and inflammatory migration of naive and activated NK subsets. Recent studies have shown that aberrant chemokine receptor expression on certain immune cells underlies the pathogenesis of clinical conditions in which recruitment of such cells is altered. A progressive accumulation of activated NK cells, subsequently resulting in the formation of chronic granoulomatous lesions in the respiratory tract and the skin, has been described in a number of TAP2-deficient patients at later stages of their disease. Therefore, the present study was set out to elucidate whether dysregulation of chemo-attracting receptors expression on NK cells could explain abnormal navigation of these cells in TAP2-deficiency. High-throughput proteomic comparison, followed by verification with flow-cytometry, revealed that chronically activated NK cells derived from three newly identified TAP2-deficient patients consistently expressed aberrant levels of CCR2 chemokine receptor in vitro and in vivo. This expression pattern translated into specific responsiveness of chronically activated NK cells derived from TAP2-deficient patients to multiple ligands of CCR2. Moreover, the in vivo elevated levels of IL-2 and MCP-1 detected in serum and bronchio-alveolar lavage samples derived from these patients highlight the potential involvement of CCR2 pathway in aberrant NK cell retention at chronic inflammatory sites.