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Tuesday, September 3, 2013

Natural killer cell interactions in adaptive immunity

This month, Deniz et al. give an overview of current knowledge about natural killer cells [NK cells] and their interface with pathways and mechanisms of adaptive immunity, with attention to allergic disease processes [J Allergy Clin Immunol 2013; 132(3):527-535]. 

The authors cover fundamentals of NK biology, such as their surface marker characterization, IFN-γ secretion, MHC class I interactions, phenotypes, tissue prevalence, cytokine profiles, and cytotoxicity to target cells.  NK cells are characterized by their cytotoxic activity through release of perforin and granzymes that are targeted at tumor cells, virally infected cells, and IgG antibody expressing cells, cytokine and chemokine secretion and signaling of adaptive immune cells, and co-stimulatory interaction with antigen presenting cells [APC] via IL-10 and TGF-β.   Deniz et al. note that NK chemokine secretion is particularly important in the co-localization and mutual maturation of dendritic cells [DC] and NK cells in areas of inflammation. 

The authors discuss the interesting parallels between NK cell subsets and T cells, noting the overlaps in surface markers and cytokine expression.  NK cells subsets consist of NK1 and NK2 cells, analogous to Th1 and Th2 cells, NK regulatory cells, NK-17 cells and NK-22.  They point out that peripheral blood mononuclear cells [PBMC] from patients with asthma showed decreased NK1 and increased NK2 levels, suggesting a NK2 bias that shadows the Th2 bias.  Also discussed was the protective effect that has been associated with NK-17 cells in rheumatoid arthritis and NK-22 cells on epithelial cell response to contact sensitivity. 

The authors discuss the limited evidence that has been reported to date on NK cell interactions in allergic diseases.  They discuss skin NK cells are known orchestration of keratinocyte apoptosis through type I cytokine signaling.  Also covered is the critical role of DCs in the evolution of NK cells.  Deniz et al report that NK cell expression and cytotoxicity is increased in patients with allergic rhinitis.  NK1 cells, but not NK2 cells, are also known to have anti-IgE activity. 

The authors conclude commenting that, while findings are limited, there is growing evidence that NK cells, like many innate immune cells, have important interactions with adaptive immune cells.  The research should now be focused to understand the characteristics of these cells in different endotypes and phenotypes of asthma, atopic dermatitis and other chronic inflammatory diseases.

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