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

IL-33 can bolster IFN- protein expression by IL-12 stimulated human NK cells 16 , but whether this enhancement occurs at level of transcription is unknown. To test this, we isolated NK cells from the blood of healthy deidentified adults prior to incubation of these cells in media containing IL-12, IL-33 or a combination of these cytokines for six hours. A concentration of 1 ng/mL of IL-12 induced a 10fold increase of IFNG expression compared to unstimulated cells, while 0.5 ng/mL of IL-12 was insufficient to induce this response (Fig. 1A) . The addition of IL-33 to NK cells cultured with either dose of IL-12 resulted in a >100-fold increase (Interaction: p<0.0001, two-way ANOVA) in IFNG mRNA expression levels ( Fig. 1A) . In a similar fashion, TNF transcript expression was increased ~2.5-fold (Interaction: p=0.0061, two-way ANOVA) by the combination of IL-12 and IL-33 in comparison to IL-12 alone (Fig. 1B) . In other types of innate lymphocytes, IL-33 can stimulate IL-5 and IL-13 expression 19 . In contrast, IL-33 alone or in combination with IL-12 had no measurable effect on expression of IL5 or IL13 expression by human NK cells (Fig. 1C) .