title: Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection.
abstract: The molecular mechanisms that drive mucosal T helper type 2 (T(H)2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell-derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T(H)2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T(H)2 responses.
authors.affiliation: Division of Immunobiology and 2 Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Reena
authors.initials: R
authors.lastname: Rani
authors.forename: Krista
authors.initials: K
authors.lastname: Dienger
authors.forename: Ian
authors.initials: I
authors.lastname: Lewkowich
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Charles
authors.initials: C
authors.lastname: Perkins
authors.forename: Lauren
authors.initials: L
authors.lastname: Lewis
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Smith
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
authors.forename: Evelyn A
authors.initials: EA
authors.lastname: Kurt-Jones
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: Umasundari
authors.initials: U
authors.lastname: Sivaprasad
authors.forename: Gurjit K
authors.initials: GK
authors.lastname: Hershey
authors.forename: De'Broski R
authors.initials: DR
authors.lastname: Herbert
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002648:Child; D006725:Hookworm Infections / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D009559:Nippostrongylus; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology; D000071164:Trefoil Factor-2
chemical_list: C506536:IL33 protein, human; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012333:RNA, Messenger; C000604007:TFF2 protein, human; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2