title: Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis.
abstract: Group 2 innate lymphoid cells (ILC2s) have an important role in acute allergic lung inflammation. Given their distribution and function, lung ILC2s are hypothesized to coordinate epithelial responses to the external environment; however, how barrier surveillance is linked to ILC2 activation remains unclear. Here, we demonstrate that alveolar type II cells are the main source of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) generated in response to chitin or migratory helminths. IL-33 and TSLP synergistically induce an interferon regulatory factor 4 (IRF4)-IL-9 program in ILC2s, and autocrine IL-9 promotes rapid IL-5 and IL-13 production required for optimal epithelial responses in the conducting airways. Thus, ILC2s link alveolar function to regulation of airway flow, revealing a key interaction between resident lymphoid and structural cells that might underlie similar organizational hierarchies in other organs.
authors.affiliation: Departments of Microbiology and Immunology and Medicine, University of California, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mohapatra
authors.affiliation: Departments of Microbiology and Immunology and Medicine, University of California, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Van Dyken
authors.affiliation: Departments of Microbiology and Immunology and Medicine, University of California, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.affiliation: Departments of Microbiology and Immunology and Medicine, University of California, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Nussbaum
authors.affiliation: Departments of Microbiology and Immunology and Medicine, University of California, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: H-E
authors.initials: HE
authors.lastname: Liang
authors.affiliation: Departments of Microbiology and Immunology and Medicine, University of California, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, California, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002686:Chitin; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000469:parasitology; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000469:parasitology; D008214:Lymphocytes / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology / Q000469:parasitology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D061251:Primary Cell Culture; D020545:Respiratory Mucosa / Q000276:immunology / Q000469:parasitology; D015398:Signal Transduction; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin; D000099218:Interferon Regulatory Factor-4
chemical_list: D002686:Chitin; D016207:Cytokines; D050835:Interferon Regulatory Factors; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D016906:Interleukin-9; D000094632:Thymic Stromal Lymphopoietin; D000099218:Interferon Regulatory Factor-4; C506535:Il33 protein, mouse