title: IL-4-producing ILC2s are required for the differentiation of TH2 cells following Heligmosomoides polygyrus infection.
abstract: Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (TH2) differentiation of CD4+T cells to elicit type-2 immunity. Despite a good understanding of the inflammatory cascade elicited following helminth infection, the initial source of IL-4 is unclear. Previous studies using the rat helminth parasite Nippostronglyus brasiliensis, identified an important role for basophil-derived IL-4 for TH2 differentiation. However, basophils are redundant for TH2 differentiation following infection with the natural helminth parasite of mice Heligmosomoides polygyrus, indicating that other sources of IL-4 are required. In this study using H. polygyrus, which is controlled by IL-4-dependent immunity, we identified that group-2 innate lymphoid cells (ILC2s) produced significant amounts of IL-4 and IL-2 following H. polygyrus infection. Leukotriene D4 was sufficient to stimulate IL-4 secretion by ILC2s, and the supernatant from activated ILC2s could potently drive TH2 differentiation in vitro in an IL-4-dependent manner. Furthermore, specific deletion of IL-4 from ILC2s compromised TH2 differentiation in vivo. Overall, this study highlights a previously unrecognized and important role for ILC2-derived IL-4 for TH2 differentiation in a natural TH2-dependent model of human helminthiasis.
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: V S
authors.initials: VS
authors.lastname: Pelly
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Kannan
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Coomes
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Entwistle
authors.affiliation: Institute of Immunology and Infection Research (3IR), University of Edinburgh, Edinburgh, UK.
authors.forename: D
authors.initials: D
authors.lastname: Rückerl
authors.affiliation: Institute of Immunity and Transplantation, UCL, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Seddon
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: MacDonald
authors.affiliation: MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: McKenzie
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006790:Host-Parasite Interactions / Q000276:immunology; D007113:Immunity, Innate; D015847:Interleukin-4 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009351:Nematospiroides dubius / Q000276:immunology*; D017206:Strongylida Infections / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D015847:Interleukin-4