title: Specification of type 2 innate lymphocytes by the transcriptional determinant Gfi1.
abstract: Type 2 innate lymphoid cells (ILC2 cells) participate in host defense against helminth parasites and in allergic inflammation. Given their functional relatedness to type 2 helper T cells (T(H)2 cells), we explored whether Gfi1 acts as a shared transcriptional determinant in ILC2 cells. Gfi1 promoted the development of ILC2 cells and controlled their responsiveness during infection with Nippostrongylus brasiliensis and protease allergen-induced lung inflammation. Gfi1 'preferentially' regulated the responsiveness of ILC2 cells to interleukin 33 (IL-33) by directly activating Il1rl1, which encodes the IL-33 receptor (ST2). Loss of Gfi1 in activated ILC2 cells resulted in impaired expression of the transcription factor GATA-3 and a dysregulated genome-wide effector state characterized by coexpression of IL-13 and IL-17. Our findings establish Gfi1 as a shared determinant that reciprocally regulates the type 2 and IL-17 effector states in cells of the innate and adaptive immune systems.
authors.affiliation: Department of Discovery Immunology, Genentech, South San Francisco, California, USA.
authors.forename: Chauncey J
authors.initials: CJ
authors.lastname: Spooner
authors.forename: Justin
authors.initials: J
authors.lastname: Lesch
authors.forename: Donghong
authors.initials: D
authors.lastname: Yan
authors.forename: Aly A
authors.initials: AA
authors.lastname: Khan
authors.forename: Alex
authors.initials: A
authors.lastname: Abbas
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ramirez-Carrozzi
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhou
authors.forename: Robert
authors.initials: R
authors.lastname: Soriano
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Eastham-Anderson
authors.forename: Lauri
authors.initials: L
authors.lastname: Diehl
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.forename: Rajita
authors.initials: R
authors.lastname: Pappu
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Jason
authors.initials: J
authors.lastname: DeVoss
authors.forename: Harinder
authors.initials: H
authors.lastname: Singh
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017206:Strongylida Infections / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C079873:Gfi1 protein, mouse; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D014157:Transcription Factors; D049452:Green Fluorescent Proteins