title: Epithelial cell-specific Act1 adaptor mediates interleukin-25-dependent helminth expulsion through expansion of Lin(-)c-Kit(+) innate cell population.
abstract: Interleukin-25 (IL-25 or IL-17E), a member of the structurally related IL-17 family, functions as an important mediator of T helper 2 cell-type (type 2) responses. We examined the cell type-specific role of IL-25-induced Act1-mediated signaling in protective immunity against helminth infection. Targeted Act1 deficiency in epithelial cells resulted in a marked delay in worm expulsion and abolished the expansion of the Lin(-)c-Kit(+) innate cell population in the mesenteric lymph node, lung, and liver. Th2 cell-inducing cytokine (IL-25 and IL-33) expression were reduced in the intestinal epithelial cells from the infected and IL-25-injected epithelial-specific Act1-deficient mice. Adoptive transfer of Lin(-)c-Kit(+) cells or combined injection of IL-25 and IL-33 restored the type 2 responses in these mice. Taken together, these results suggest that epithelial-specific Act1 mediates the expansion of the Lin(-)c-Kit(+) innate cell population through the positive-feedback loop of IL-25, initiating the type 2 immunity against helminth infection.
authors.affiliation: Department of Immunology, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Kang
authors.forename: Shadi
authors.initials: S
authors.lastname: Swaidani
authors.forename: Weiguo
authors.initials: W
authors.lastname: Yin
authors.forename: Chenhui
authors.initials: C
authors.lastname: Wang
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Barlow
authors.forename: Muhammet Fatih
authors.initials: MF
authors.lastname: Gulen
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bulek
authors.forename: Jeong-su
authors.initials: JS
authors.lastname: Do
authors.forename: Mark
authors.initials: M
authors.lastname: Aronica
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Booki
authors.initials: B
authors.lastname: Min
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006373:Helminthiasis / Q000276:immunology* / Q000378:metabolism; D006376:Helminths / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007378:Interleukins; C442281:Mydgf protein, mouse; C515963:Traf3ip2 protein, mouse