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 language | English |
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Journal | PLoS Pathogens |
Volume | 14 |
Issue number | 11 |
DOIs | |
Publication status | Published - 30 Nov 2018 |
Bibliographical note
AcknowledgmentsThe authors gratefully thank Stella Pearson, Brian Chan and Yvonne Harcus for excellent technical assistance, as well as Professor Rick M Maizels for the kind provision of Nippostrongylus brasiliensis and Dr. Martin Waterfall and Dr. Gareth Howell for flow cytometry support. The authors also thank Biological Services Facility staff at the University of Edinburgh and the University of Manchester, for help with animal husbandry. TES acknowledges the support of the Manchester Collaborative Centre for Inflammation Research, a joint venture between The University of Manchester and GlaxoSmithKline.
Keywords
- Animals
- Intercellular Signaling Peptides and Proteins/metabolism
- Lectins/metabolism
- Lung/immunology
- Mice
- Inbred BALB C
- Inbred C57BL
- Knockout
- Nematode Infections/immunology
- Nippostrongylus/immunology
- Receptors
- Cell Surface/deficiency
- Signal Transduction
- Strongylida Infections/immunology
- beta-N-Acetylhexosaminidases/metabolism