Chemokine Receptor Expression on Normal Blood CD56⁺NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population

Abstract

Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal blood CD56+low CD16+ and CD56+high CD16−/+low NK-cells. Conventional CD56+low and CD56+high NK-cells present in the normal PB do express CKR for inflammatory cytokines, although with different patterns CD56+low NK-cells are mainly CXCR1/CXCR2+ and CXCR3/CCR5−/+, whereas mostly CD56+high NK-cells are CXCR1/CXCR2− and CXCR3/CCR5+. Both NK-cell subsets have variable CXCR4 expression and are CCR4− and CCR6−. The CKR repertoire of the CD56+low NK-cells approaches to that of neutrophils, whereas the CKR repertoire of the CD56+high NK-cells mimics that of Th1+ T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we named CD56+int NK-cells. These NK-cells are CXCR3/CCR5+, they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57− and CD158a−. In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-known CD56+high and CD56+low NK-cells populations.

The Role of CXC Chemokine Receptors 1–4 on Immune Cells in the Tumor Microenvironment

“…CXCR1 and CXCR2 are highly expressed by cytotoxic CD56 dim NK cells ( 37 , 38 ). We recently showed that CXCR2 expression is downregulated on tumor-infiltrating NK cells in RCC and genetic modification to re-express CXCR2 enhanced recruitment of NK cells to the tumor site ( 39 ).…”

“…CXCR3 is expressed on different subtypes of T and NK cells ( 37 , 44 ) and binds to CXCL9, CXCL10, and CXCL11. During homeostasis, CXCL9, CXCL10 and CXCL11 are expressed at low levels by monocytes, endothelial cells and fibroblasts, but are upregulated upon cytokine stimulation, especially by IFNγ and TNFα ( 45 , 46 ).…”

Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection

“…This receptor is expressed on several immune cells, including activated T cells [40][41][42][43], dendritic cells [79,80] and NK cells [81], but not on resting T cells, B cells, monocytes, or granulocytes [34]. Non-immune cells such as fibroblasts, endothelial, epithelial and smooth-muscle cells also express this receptor [38,82].…”

Human innate immune cell crosstalk induces melanoma cell senescence

“…13 For instance, the IL-8 chemokine receptors CXCR1 and CXCR2 are expressed on CD56 dim CD16 + NK cells and mediate recruitment into tissues. 14,15 NK cells are known for exerting direct perforin/ granzyme B-mediated cytotoxicity against tumor cells in the tissue. Alternatively, it was recently reported that NK cell cytokine secretion can arrest tumor cell growth through sensing of PDGF-DD via Nkp44 on NK cells.…”