Abstract Dissemination of type 2 immunity along skin-gut-lung axes contributes to allergic march progressions in atopic individuals, yet the underlying mechanisms remain incompletely understood. In mice, gastrointestinal helminth infections can mobilize a circulating pool of gut-derived, inflammatory type 2 innate lymphoid cells (iILC2s), which in turn establish an early type 2 immune response in remote lung. Here, using the model allergen ovalbumin (OVA), we demonstrate duodenum-restricted expansion of iILC2s is similarly elicited in response to an ingested food allergen. Gut-derived iILC2s migrated to mesenteric lymph nodes (MLNs) and lung, wherein they positively correlated with local lung Il13 expression within one hour of food allergen ingestion. Duodenal iILC2 expansion was accompanied by duodenal tuft cell expansion and IL-25 production, and treatment with IL-25 recapitulated iILC2 expansion and lung migration in the absence of allergen. Inhibition of iILC2 migration attenuated the rapid food allergen- or IL-25-induced Il13 response and subsequent mucin dysregulation in remote lung. Eosinophil infiltration proceeded iILC2s into remote lungs by 24 hours; however, neither pharmacologic nor genetic inhibition of iILC2s prevented food allergen- or IL-25-elicited eosinophil remote lung homing, decoupling eosinophil recruitment from iILC2s. Collectively, these data shed new light on type 2 immune dissemination along the gut-lung axis by revealing the duodenum as a regional hub for food allergen-driven expansion of iILC2s that rapidly reshape the remote lung cytokine milieu.
Falta et al. (Tue,) studied this question.
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