title: Nonredundant roles for B cell-derived IL-10 in immune counter-regulation.
abstract: IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among IL-10-expressing cells in peripheral lymphoid tissues at baseline and during diverse models of in vivo immunological challenge. Use of a novel B cell-specific IL-10 knockout mouse revealed that B cell-derived IL-10 nonredundantly decreases virus-specific CD8(+) T cell responses and plasma cell expansion during murine cytomegalovirus infection and modestly restrains immune activation after challenge with foreign Abs to IgD. In contrast, no role for B cell-derived IL-10 was evident during endotoxemia; however, although B cells dominated lymphoid tissue IL-10 production in this model, myeloid cells were dominant in blood and liver. These data suggest that B cells are an underappreciated source of counter-regulatory IL-10 production in lymphoid tissues, provide a clear rationale for testing the biological role of B cell-derived IL-10 in infectious and inflammatory disease, and underscore the utility of cell type-specific knockouts for mechanistic limning of immune counter-regulation.
authors.affiliation: Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Madan
authors.forename: Filiz
authors.initials: F
authors.lastname: Demircik
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Surianarayanan
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Allen
authors.forename: Senad
authors.initials: S
authors.lastname: Divanovic
authors.forename: Aurelien
authors.initials: A
authors.lastname: Trompette
authors.forename: Nir
authors.initials: N
authors.lastname: Yogev
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gu
authors.forename: Marat
authors.initials: M
authors.lastname: Khodoun
authors.forename: David
authors.initials: D
authors.lastname: Hildeman
authors.forename: Nicholas
authors.initials: N
authors.lastname: Boespflug
authors.forename: Mariela B
authors.initials: MB
authors.lastname: Fogolin
authors.forename: Lothar
authors.initials: L
authors.lastname: Gröbe
authors.forename: Marina
authors.initials: M
authors.lastname: Greweling
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Rhonda
authors.initials: R
authors.lastname: Cardin
authors.forename: Markus
authors.initials: M
authors.lastname: Mohrs
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Karp
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology; D041681:NIH 3T3 Cells
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016753:Interleukin-10