title: IL-17C regulates the innate immune function of epithelial cells in an autocrine manner.
abstract: Interleukin 17C (IL-17C) is a member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. Here we show that IL-17C functioned in a unique autocrine manner, binding to a receptor complex consisting of the receptors IL-17RA and IL-17RE, which was preferentially expressed on tissue epithelial cells. IL-17C stimulated epithelial inflammatory responses, including the expression of proinflammatory cytokines, chemokines and antimicrobial peptides, which were similar to those induced by IL-17A and IL-17F. However, IL-17C was produced by distinct cellular sources, such as epithelial cells, in contrast to IL-17A, which was produced mainly by leukocytes, especially those of the T(H)17 subset of helper T cells. Whereas IL-17C promoted inflammation in an imiquimod-induced skin-inflammation model, it exerted protective functions in dextran sodium sulfate-induced colitis. Thus, IL-17C is an essential autocrine cytokine that regulates innate epithelial immune responses.
authors: Department of Immunology, Genentech, South San Francisco, California, USA.
authors: Vladimir
authors: V
authors: Ramirez-Carrozzi
authors: Arivazhagan
authors: A
authors: Sambandam
authors: Elizabeth
authors: E
authors: Luis
authors: Zhongua
authors: Z
authors: Lin
authors: Surinder
authors: S
authors: Jeet
authors: Justin
authors: J
authors: Lesch
authors: Jason
authors: J
authors: Hackney
authors: Janice
authors: J
authors: Kim
authors: Meijuan
authors: M
authors: Zhou
authors: Joyce
authors: J
authors: Lai
authors: Zora
authors: Z
authors: Modrusan
authors: Tao
authors: T
authors: Sai
authors: Wyne
authors: W
authors: Lee
authors: Min
authors: M
authors: Xu
authors: Patrick
authors: P
authors: Caplazi
authors: Lauri
authors: L
authors: Diehl
authors: Jason
authors: J
authors: de Voss
authors: Mercedesz
authors: M
authors: Balazs
authors: Lino
authors: L
authors: Gonzalez
authors: Harinder
authors: H
authors: Singh
authors: Wenjun
authors: W
authors: Ouyang
authors: Rajita
authors: R
authors: Pappu
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D020381:Interleukin-17 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011485:Protein Binding; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17