Mapping the cellular source and role of IL-22 in murine lung infections

Interleukin-22 (IL-22) belongs to the IL-10 cytokine family and is expressed in the lung during infection with Chlamydia muridarum (Cmu) and Pneumonia Virus of Mice (PVM). IL-22 can have both pro-inflammatory and tissue protective roles depending on the inflammatory context, tissue tropisms, and local cytokine milieu. Several cell types can produce IL-22, including innate lymphoid cells, neutrophils, γδ T cells, and CD4⁺ Th cells. While IL-22 has previously been associated with Th17 cells, recently a novel lineage of CD4⁺ T helper cells (known as Th22 cells) have been identified that predominantly produce IL-22 in the absence of IL-17. Current knowledge of the cellular source of IL-22 in inflammatory lung infections is unclear and our understanding of a role for IL-22 in the pathogenesis of these diseases remains limited. We have mapped, for the first time, the cellular source of IL-22 in both Cmu and PVM lung infections using novel transgenic dual reporter mice. We show that IL-22 expression only partially overlaps with IL-17a expression and identify Th22 cells as the major source of IL-22 in the lung. Using IL-22 deficient mice, we show a functional role for IL-22 in Cmu infection, but fail to identify a role in PVM infection. Our study provides novel insight into the cellular source of IL-22 in the context of lung infections and identifies a role for IL-22 in Cmu lung infection.