IL-17A moonlighting in lung type 2 immunity.

Abstract

Both Type 2 inflammation and the cytokine IL-17A are implicated in allergic asthma, yet how these distinct immune responses are interlinked in the lung remains poorly understood. Utilizing helminth infection models in mice to induce pulmonary Type 2 immunity, Ajendra et al. reveal a molecular switch, where IL-17A initially acts to promote the establishment of the Type 2 response to infection by inhibiting IFNγ production, but at later stages IL- 17A acts to reduce Type 2 responses, protecting the lung tissue from detrimental chronic inflammation. Interestingly, the multitasking function of IL-17A in regulating lung Type 2 inflammation was even observed when mice were infected with a different helminth species that resides entirely in the gastrointestinal tract. These novel findings advance our understanding of how IL-17A plays multiple “moonlighting” functions in regulating pulmonary Type 2 inflammation, which has implications for the etiology of severe asthma.