The role of ILC2s in neonatal type 2 immunity bias and allergen sensitization

Abstract

Abstract Neonatal immunity is largely type 2, potentially dampening damaging inflammatory type 1 immunity. Without early correction from gradual microbial type 1 stimulation, type 2 immunity may become overactive, resulting in allergic disease. Exposure to inhaled allergens during the neonatal period may sensitize individuals resulting in the development of allergic lung disease. Our lab has characterized group 2 innate lymphoid cells (ILC2s) in mouse lungs, which upon exposure to inhaled allergens, produce IL-5 and IL-13 and drive type 2 lung inflammation. We investigated whether ILC2s play a role in neonatal type 2 bias and allergen sensitization. Mouse lung ILC2s rapidly develop and 10 day old (D10) pups had more ILC2s than adults. D10 ILC2s appeared to be activated due to intracellular IL-13 and IL-5 expression and eosinophil lung infiltration, not observed in ILC2-deficient pups. ILC2 numbers are high in D10 lung-draining lymph nodes but not in the spleen or liver. ILC2s may be driving Th2-biased cell differentiation, as intranasal (IN) OVA-antigen treatment into D10 OTII pups results in significantly more IL-4+IL-13+ CD4+ T cells in the lung-draining LN after 6 days compared to adult OTII mice. Moreover, upon IN protease-allergen papain treatment at D10 and then again 4 weeks later, higher numbers of LN Th2 cells were present compared to similarly treated adults. Importantly, IL-33-deficient D10 pups, had fewer activated ILC2s and little eosinophil lung infiltration, suggesting that neonatal ILC2s activated by endogenous IL-33, produce type 2 cytokines resulting in type 2-biased lung immunity. Therefore, ILC2s may play a role in the neonatal sensitization of individuals, causing the development of allergic lung inflammation in adults.