Type-2 innate lymphoid cells facilitate antigen-induced CD4+ TH2 cell immune response that exacerbates chronic allergic asthma (HYP7P.291)

Abstract

Type-2 innate lymphoid cells (ILC2s) and acquired CD4+TH2 and TH17 cells were shown to contribute to the pathogenesis of allergic asthma; however, their relative roles in mounting antigen recall response that exacerbate chronic allergic asthma remain elusive. Here we reported that repeated OVA re-challenge induced significant increases of eosinophil, not neutrophil accumulation and serum OVA specific IgE and IgG1 in rested mice that previously developed allergic asthma. Subsequent analysis revealed that these rested mice with allergic asthma preferentially mounted elevated OVA specific CD4+TH2 cell response against intranasal OVA re-challenge, while the frequency of lung OVA specific TH17 cells or ILC2s remained constant. While ILC2s and TH17 cells developed normally, STAT6 KO mice that lacked TH2 cell compartment or mice ablated of CD4+ T cells failed to mount allergic recall response to OVA re-challenge. Notably, we observed that cocultured ILC2s could greatly enhance TH2 cytokine production by OVA specific TH2 cells after OVA stimulation ex vivo. Indeed, mice co-transferred with ILC2s and OVA specific TH2 cells exhibited significantly increased inflammatory cell infiltration and goblet cell hyperplasia, compared to those transferred with ILC2s or TH2 cells alone. Collectively, our results suggest that antigen re-exposures preferentially induce lung resident TH2 cells to mount antigen recall immune response that can be enhanced by ILC2s to exacerbate allergic inflammation