Cytokine-induced cytokine production by conventional and innate lymphoid cells

Innate immune and differentiated T cells produce signature cytokines in response to cytokine stimulation. Optimal production requires stimulation by an NF-κB inducer, most commonly an interleukin (IL)-1 family member, and a STAT activator. Usually, there is linkage between the IL-1 family member, the activated STAT and the cytokines produced: IFNγ producers respond to the IL-1 family member, IL-18 and IL-12, a STAT4 activator; IL-13 producers respond to IL-33 (although for ILC2 cells this may be replaced by IL-25) and STAT5 activators; for cells producing IL-17A or IL-22, the combination is IL-1 and a STAT3 inducer. Cytokine-induced cytokine production may have broad significance in orchestrating innate responses to distinct infectious agents and in maintaining inflammatory responses after elimination of the inciting antigen.