Non-redundant roles for ILC2 and TH2 cells during anamnestic lung Type 2 immunity

Type 2 immune responses help with wound healing and clearing helminth infections, but the distinct roles of group 2 innate lymphoid cells (ILC2s) and T-helper 2 (TH2) cells are not fully understood. In this study, we examined whether ILC2s and TH2 cells are necessary or sufficient to repair lung injury and prevent re-infection with the parasite Nippostrongylus brasiliensis. Surprisingly, removing TH2 cells before re-infection did not affect lung healing or worm clearance. However, mice lacking ILC2s (LCR1-/-) showed severe IL-17-related lung bleeding and poor parasite clearance. Activated ILC2s expressed high levels of Amphiregulin (Areg) and Tph1, and Areg+ ILC2s were more abundant than TH2 cells in re-infected lungs. Although treatment with recombinant Areg increased TH2 cell numbers and improved worm clearance, it did not reduce lung injury in ILC2-deficient mice. Interestingly, serotonin levels influenced IL-17-driven lung damage regardless of parasite burden. Our findings suggest that while TH2 cells help fight infection, ILC2s play a unique and essential role in repairing lung tissue.