Ym1 induces RELMα and rescues IL-4Rα deficiency in lung repair during nematode infection

Tara E. Sutherland*, Dominik Rückerl, Nicola Logan, Sheelagh Duncan, Thomas A. Wynn, Judith E. Allen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Ym1 and RELMα are established effector molecules closely synonymous with Th2-type inflammation and associated pathology. Here, we show that whilst largely dependent on IL-4Rα signaling during a type 2 response, Ym1 and RELMα also have IL-4Rα-independent expression patterns in the lung. Notably, we found that Ym1 has opposing effects on type 2 immunity during nematode infection depending on whether it is expressed at the time of innate or adaptive responses. During the lung migratory stage of Nippostrongylus brasiliensis, Ym1 promoted the subsequent reparative type 2 response but once that response was established, IL-4Rα-dependent Ym1 was important for limiting the magnitude of type 2 cytokine production from both CD4+ T cells and innate lymphoid cells in the lung. Importantly, our study demonstrates that delivery of Ym1 to IL-4Rα deficient animals drives RELMα production and overcomes lung repair deficits in mice deficient in type 2 immunity. Together, Ym1 and RELMα, exhibit time and dose-dependent interactions that determines the outcome of lung repair during nematode infection.

Original languageEnglish
Article numbere1007423
Number of pages27
JournalPLoS Pathogens
Volume14
Issue number11
DOIs
Publication statusPublished - 30 Nov 2018

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