Work

ILC2 and TH2 cells serve non redundant roles during anamnestic lung Type 2 immunity 2116

Year: 2025

Type: article

Abstract: Description Lung anti-helminth immunity elicited by memory type 2 cytokine responses promotes wound healing as well as trapping and elimination of migratory larvae. However, the relative contribution(s) of group 2 innate lymphoid (ILC2s) vs. T-helper 2 (TH2) populations to these effects remain unclear. This study demonstrates that although CD4+ T cells were necessary for pulmonary IL-5/IL-13+ ILC2 accumulation, worm clearance, and tissue repair; their depletion only before secondary challenge did not alter these responses. Conversely, mice deficient in locus control region 1 (LCR1-/-), which selectively lack ILC2s, experience impaired TH2 cell expansion, larval killing, and pulmonary tissue repair, associated with elevated IL-17+ gdT cells and neutrophils upon secondary challenge. Although adoptive transfer of CD4+ T cells into LCR1-/- mice restored larval killing, it failed to promote lung repair or suppress gdT cell-driven neutrophilic inflammation. ILC2s from secondary infected mice were enriched on amphiregulin (Areg) and tryptophan hydroxylase 1 expression, which catalyzes serotonin biosynthesis. Areg treatment rescued parasite clearance and TH2 cells in LCR1-/- mice, whereas serotonin reduced lung haemorrhage and IL-17+ gd T cells in the absence of CD4+ T cells. This work reveals a division of labor between TH2 cells and ILC2s wherein ILC2s and TH2 cells redundantly mediate larval killing and ILC2s alone limit IL-17+gd T cells and promote tissue repair. Funding Sources U01 AI163062-01; RO1 AI123173-05 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.080