Interleukin-33 promotes type 1 cytokine expression via p38 MAPK in human natural killer cells

David E. Ochayon; Ayad Ali; Pablo C. Alarcon; Durga Krishnamurthy; Leah C. Kottyan; Michael Borchers; Stephen N. Waggoner

In pathologies such as asthma and COPD, IL-33 play a central role in disease pathology, those pathologies were shown to be exacerbated by respiratory viral infection which mediates the release of type 1 cytokines such as IL-12 [40] [41] [42] [43] . Thus, we speculate that NK cells derived from the blood or tissues of patients exhibiting elevated levels of IL-33 would be more sensitive to ex vivo IL-12 stimulation. As an example, cigarette smoke induces epithelial damage resulting in increased expression of IL-33 17, 42 , which provokes hypersensitive IFNγ production by mouse NK cells in response to IL-12 44 . Our initial data suggest that NK cells from smokers exhibit greater sensitivity to IL-12 in terms of IFN- expression than NK cells derived from healthy, non-smokers (D.O., M.B., and S.N.W unpublished observations). We speculate that elevated IL-33 levels in smokers or asthmatic patients provokes hypersensitivity to type 1 inflammatory cues triggered by virus infection. Thus, smokers exposed to virus infections likely produce high, potentially pathogenic expression of IFN-. Our findings provide new insights about potential functional hypersensitivity of NK cells in type 2 cytokine rich inflammatory milieus such as asthma and COPD as well as in smokers.