title: IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation.
abstract: IL-9 fate reporter mice established type 2 innate lymphoid cells (ILC2s) as major producers of this cytokine in vivo. Here we focus on the role of IL-9 and ILC2s during the lung stage of infection with Nippostrongylus brasiliensis, which results in substantial tissue damage. IL-9 receptor (IL-9R)-deficient mice displayed reduced numbers of ILC2s in the lung after infection, resulting in impaired IL-5, IL-13, and amphiregulin levels, despite undiminished numbers of Th2 cells. As a consequence, the restoration of tissue integrity and lung function was strongly impaired in the absence of IL-9 signaling. ILC2s, in contrast to Th2 cells, expressed high levels of the IL-9R, and IL-9 signaling was crucial for the survival of activated ILC2s in vitro. Furthermore, ILC2s in the lungs of infected mice required the IL-9R to up-regulate the antiapoptotic protein BCL-3 in vivo. This highlights a unique role for IL-9 as an autocrine amplifier of ILC2 function, promoting tissue repair in the recovery phase after helminth-induced lung inflammation.
authors.affiliation: Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London NW7 1AA, England, UK.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Morrison
authors.forename: Christoph
authors.initials: C
authors.lastname: Wilhelm
authors.forename: Mark
authors.initials: M
authors.lastname: Wilson
authors.forename: Helena
authors.initials: H
authors.lastname: Ahlfors
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.forename: Helena
authors.initials: H
authors.lastname: Helmby
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
mesh_terms: D066258:Amphiregulin; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D066255:EGF Family of Proteins; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology / Q000469:parasitology*; D008214:Lymphocytes / Q000166:cytology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009559:Nippostrongylus; D011014:Pneumonia / Q000276:immunology / Q000469:parasitology*; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology
chemical_list: D066258:Amphiregulin; C587849:Areg protein, mouse; D016207:Cytokines; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D016906:Interleukin-9