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

PLoS Pathog. 2018 Nov 30;14(11):e1007423. doi: 10.1371/journal.ppat.1007423. eCollection 2018 Nov.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lectins / metabolism*
  • Lung / immunology
  • Lung / metabolism
  • Lung / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nematode Infections / immunology
  • Nematode Infections / metabolism*
  • Nippostrongylus / immunology
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / metabolism
  • Signal Transduction
  • Strongylida Infections / immunology
  • Strongylida Infections / metabolism
  • beta-N-Acetylhexosaminidases / metabolism*


  • Il4ra protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Lectins
  • Receptors, Cell Surface
  • Retnla protein, mouse
  • Chil3 protein, mouse
  • beta-N-Acetylhexosaminidases