title: Collaborative interactions between type 2 innate lymphoid cells and antigen-specific CD4+ Th2 cells exacerbate murine allergic airway diseases with prominent eosinophilia.
abstract: Type-2 innate lymphoid cells (ILC2s) and the acquired CD4(+) Th2 and Th17 cells contribute to the pathogenesis of experimental asthma; however, their roles in Ag-driven exacerbation of chronic murine allergic airway diseases remain elusive. In this study, we report that repeated intranasal rechallenges with only OVA Ag were sufficient to trigger airway hyperresponsiveness, prominent eosinophilic inflammation, and significantly increased serum OVA-specific IgG1 and IgE in rested mice that previously developed murine allergic airway diseases. The recall response to repeated OVA inoculation preferentially triggered a further increase of lung OVA-specific CD4(+) Th2 cells, whereas CD4(+) Th17 and ILC2 cell numbers remained constant. Furthermore, the acquired CD4(+) Th17 cells in Stat6(-/-)/IL-17-GFP mice, or innate ILC2s in CD4(+) T cell-ablated mice, failed to mount an allergic recall response to OVA Ag. After repeated OVA rechallenge or CD4(+) T cell ablation, the increase or loss of CD4(+) Th2 cells resulted in an enhanced or reduced IL-13 production by lung ILC2s in response to IL-25 and IL-33 stimulation, respectively. In return, ILC2s enhanced Ag-mediated proliferation of cocultured CD4(+) Th2 cells and their cytokine production, and promoted eosinophilic airway inflammation and goblet cell hyperplasia driven by adoptively transferred Ag-specific CD4(+) Th2 cells. Thus, these results suggest that an allergic recall response to recurring Ag exposures preferentially triggers an increase of Ag-specific CD4(+) Th2 cells, which facilitates the collaborative interactions between acquired CD4(+) Th2 cells and innate ILC2s to drive the exacerbation of a murine allergic airway diseases with an eosinophilic phenotype.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45220;
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45220;
authors.forename: Jee-Boong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Division of Hematology, Oncology, and Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH 43205; and.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45220.
authors.forename: Gurjit K Khurana
authors.initials: GK
authors.lastname: Hershey
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45220; yui_hsi.wang@cchmc.org.
authors.forename: Yui-Hsi
authors.initials: YH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000633:toxicity; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; C442281:Mydgf protein, mouse; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D010047:Ovalbumin