- Authors: Sutherland, T. E., Ruckerl, D., Logan, N., Duncan, S., Wynn, T. A., Allen, J. E.
- Year: 2018
- Journal: PLoS Pathog 14 e1007423
- Applications: in vivo / DNA / in vivo-jetPEI
Wild-type BALB/c mice were administered 20 μg plasmid complexed with in vivo JetPEI intranasally. Bronchoalveolar Lavage of lungs was performed 48 h after transfection.
Ym1 and RELMalpha are established effector molecules closely synonymous with Th2-type inflammation and associated pathology. Here, we show that whilst largely dependent on IL-4Ralpha signaling during a type 2 response, Ym1 and RELMalpha also have IL-4Ralpha-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-4Ralpha-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-4Ralpha deficient animals drives RELMalpha production and overcomes lung repair deficits in mice deficient in type 2 immunity. Together, Ym1 and RELMalpha, exhibit time and dose-dependent interactions that determines the outcome of lung repair during nematode infection.