title: Reciprocal regulation of lymphoid tissue development in the large intestine by IL-25 and IL-23.
abstract: Isolated lymphoid follicles (ILFs) develop after birth in the small and large intestines (SI and LI) and represent a dynamic response of the gut immune system to the microbiota. Despite their similarities, ILF development in the SI and LI differs on a number of levels. We show that unlike ILF in the SI, the microbiota inhibits ILF development in the colon as conventionalization of germ-free mice reduced colonic ILFs. From this, we identified a novel mechanism regulating colonic ILF development through the action of interleukin (IL)-25 on IL-23 and its ability to modulate T regulatory cell (Treg) differentiation. Colonic ILF develop in the absence of a number of factors required for the development of their SI counterparts and can be specifically suppressed by factors other than IL-25. However, IL-23 is the only factor identified that specifically promotes colonic ILFs without affecting SI-ILF development. Both IL-23 and ILFs are associated with inflammatory bowel disease, suggesting that disruption to this pathway may have an important role in the breakdown of microbiota-immune homeostasis.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Donaldson
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Bradford
authors.affiliation: Department of Microbiology and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: D
authors.initials: D
authors.lastname: Artis
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Mabbott
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007420:Intestine, Large / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D053759:Interleukin-23; D007378:Interleukins; C442281:Mydgf protein, mouse