title: ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation.
abstract: Innate lymphoid cells (ILCs) contribute to host defence and tissue repair but can induce immunopathology. Recent work has revealed tissue-specific roles for ILCs; however, the question of how a small population has large effects on immune homeostasis remains unclear. We identify two mechanisms that ILC3s utilise to exert their effects within intestinal tissue. ILC-driven colitis depends on production of granulocyte macrophage-colony stimulating factor (GM-CSF), which recruits and maintains intestinal inflammatory monocytes. ILCs present in the intestine also enter and exit cryptopatches in a highly dynamic process. During colitis, ILC3s mobilize from cryptopatches, a process that can be inhibited by blocking GM-CSF, and mobilization precedes inflammatory foci elsewhere in the tissue. Together these data identify the IL-23R/GM-CSF axis within ILC3 as a key control point in the accumulation of innate effector cells in the intestine and in the spatio-temporal dynamics of ILCs in the intestinal inflammatory response.
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Pearson
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Thornton
authors.affiliation: CSL Ltd., Parkville, Australia.
authors.forename: Brent
authors.initials: B
authors.lastname: McKenzie
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Schaupp
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicky
authors.initials: N
authors.lastname: Huskens
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Thibault
authors.initials: T
authors.lastname: Griseri
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: West
authors.affiliation: Division of Immune Cell Biology, National Institute for Medical Research, London, United Kingdom.
authors.forename: Sim
authors.initials: S
authors.lastname: Tung
authors.affiliation: Division of Immune Cell Biology, National Institute for Medical Research, London, United Kingdom.
authors.forename: Benedict P
authors.initials: BP
authors.lastname: Seddon
authors.affiliation: Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.|Department of Paediatrics, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Holm H
authors.initials: HH
authors.lastname: Uhlig
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.|Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
mesh_terms: D003092:Colitis / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*
chemical_list: C508840:IL23A protein, human; D053760:Interleukin-23 Subunit p19; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: colitis; human; immunology; innate lymphoid cells; live imaging; mouse; mucosal immunology