title: IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis.
abstract: Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.
authors.affiliation: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Armstrong
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Barlow
authors.forename: Sean P
authors.initials: SP
authors.lastname: Saunders
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
authors.forename: Gordon
authors.initials: G
authors.lastname: Cooke
authors.forename: Ruairi J
authors.initials: RJ
authors.lastname: Fahy
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Crotty
authors.forename: Nikhil
authors.initials: N
authors.lastname: Hirani
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Flynn
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D000368:Aged; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology; D007113:Immunity, Innate; D007249:Inflammation; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008099:Liver / Q000469:parasitology; D008168:Lung / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D012550:Schistosoma mansoni
chemical_list: D015815:Cell Adhesion Molecules; C486701:IL25 protein, human; D018793:Interleukin-13; D020381:Interleukin-17; D007378:Interleukins; C442281:Mydgf protein, mouse; C512835:POSTN protein, human; C082838:Postn protein, mouse; D003094:Collagen
keywords: cytokine; inflammation; innate response; therapy