?d T cells orchestrate the induction of protective type 2 immunity in neonatal influenza infection

Influenza infection causes high rates of hospitalization and mortality in infants. ?d T cells are critical for immune responses against pathogens as regulators and effectors, especially in infants, and yet the roles of neonatal ?d T cells in influenza remain to be investigated. Here we report that ?d T cells were protective against mortality associated with neonatal influenza infection. Infection induced the accumulation and activation of ?d T cells, which transiently expressed IL-17a to enhance early IL-33 production by lung epithelial cells via STAT3 phosphorylation. Subsequently, this led to type 2 immune responses with elicited infiltration of ILC2s and Tregs resulting in increased amphiregulin secretion and tissue repair. Loss of ?d T cells did not alter viral clearance or IFN-? production. Thus, our results identify a specific requirement for ?d T cells in influenza-infected neonates by initiating type 2 immune responses, mediating tissue homeostasis, and promoting lung integrity. Overall design: RNA-Seq of total RNA from whole-lung homogenates of influenza-infected wild-type and TCRd-/- neonatal mice at 8 days post infection.