Functional aberrant expression of CCR2 receptor on chronically activated NK cells in patients with TAP-2 deficiency

Jacob Hanna, Huda Mussaffi, Guy Steuer, Suhair Hanna, Maher Deeb, Hannah Blau, Tal I. Arnon, Noam Weizman, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Chemokines play a pivotal role in homeostatic and inflammatory migration of naive and activated natural killer (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. Progressive accumulation of activated NK cells, subsequently resulting in the formation of chronic granulomatous lesions in the respiratory tract and the skin, has been described in a number of patients with transporter associated with antigen processing 2 (TAP-2) deficiency in the later stages of disease. Therefore, the goal of the present study was to elucidate whether the dysregulation of chemoattracting receptor expression on NK cells could explain abnormal navigation of these cells in TAP-2 deficiency. High-throughput proteomic comparison, followed by verification with flow cytometry, revealed that chronically activated NK cells derived from 3 newly identified patients with TAP-2 deficiency consistently expressed aberrant levels of CC chemokine receptor 2 (CCR2) chemokine receptor in vitro and in vivo. This expression pattern translated into specific responsiveness of chronically activated NK cells derived from patients with TAP-2 deficiency to multiple ligands of CCR2. Moreover, the in vivo elevated levels of interleukin-2 (IL-2) and monocyte chemoattractant protein-1 (MCP-1) detected in serum and bronchoalveolar lavage samples derived from these patients highlight the potential involvement of the CCR2 pathway in aberrant NK-cell retention at chronic inflammatory sites.

Original languageAmerican English
Pages (from-to)3465-3473
Number of pages9
JournalBlood
Volume106
Issue number10
DOIs
StatePublished - 15 Nov 2005

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