title: Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection.
abstract: Th17-driven immune responses contribute to the pathogenesis of many chronic inflammatory diseases. In this study, we investigated the role of IL-17 signaling in chronic gastric inflammation induced by Helicobacter pylori, a Gram-negative bacterium that persistently colonizes the human stomach. Wild-type C57BL/6 mice and mice lacking IL-17RA (IL-17RA(-/-)) were orogastrically infected with H. pylori. Differences in bacterial colonization density and gastric inflammation were not apparent at 1 mo postinfection, but by 3 mo postinfection, H. pylori colonization density was higher and mononuclear gastric inflammation more severe in infected IL-17RA(-/-) mice than in infected wild-type mice. A striking feature was a marked increase in gastric B cells, plasma cells, and lymphoid follicles, along with enhanced H. pylori-specific serum Ab responses, in infected IL-17RA(-/-) mice. Fewer gastric neutrophils and lower levels of neutrophil-recruiting chemokines were detected in infected IL-17RA(-/-) mice than in infected wild-type mice. Gastric IL-17a and IL-21 transcript levels were significantly higher in infected IL-17RA(-/-) mice than in infected wild-type mice or uninfected mice, which suggested that a negative feedback loop was impaired in the IL-17RA(-/-) mice. These results underscore an important role of IL-17RA signaling in regulating B cell recruitment. In contrast to many chronic inflammatory diseases in which IL-17RA signaling promotes an inflammatory response, IL-17RA signaling down-regulates the chronic mononuclear inflammation elicited by H. pylori infection.
authors.affiliation: Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA. holly.m.algood@vanderbilt.edu
authors.forename: Holly M Scott
authors.initials: HM
authors.lastname: Algood
authors.forename: Shannon Sedberry
authors.initials: SS
authors.lastname: Allen
authors.forename: Mary K
authors.initials: MK
authors.lastname: Washington
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Geraldine G
authors.initials: GG
authors.lastname: Miller
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: C491673:Il17ra protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D053722:Receptors, Interleukin-17