title: Immune Complexes Indirectly Suppress the Generation of Th17 Responses In Vivo.
abstract: The precise context in which the innate immune system is activated plays a pivotal role in the subsequent instruction of CD4+ T helper (Th) cell responses. Th1 responses are downregulated when antigen is encountered in the presence of antigen-IgG immune complexes. To assess if Th17 responses to antigen are subject to similar influences in the presence of immune complexes we utilized an inflammatory airway disease model in which immunization of mice with Complete Freund's Adjuvant (CFA) and ovalbumin (Ova) induces a powerful Ova-specific Th1 and Th17 response. Here we show that modification of that immunization with CFA to include IgG-Ova immune complexes results in the suppression of CFA-induced Th17 responses and a concurrent enhancement of Ova-specific Th2 responses. Furthermore, we show the mechanism by which these immune complexes suppress Th17 responses is through the enhancement of IL-10 production. In addition, the generation of Th17 responses following immunization with CFA and Ova were dependent on IL-1α but independent of NLRP3 inflammasome activation. Together these data represent a novel mechanism by which the generation of Th17 responses is regulated.
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Ceren
authors.initials: C
authors.lastname: Ciraci
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Janczy
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Jain
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Haasken
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cyntia
authors.initials: C
authors.lastname: Pecli E Silva
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Benjamim
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Sadler
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Yamasaki 2669, Noda, Chiba, 278-0022, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama, 332-0012, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Lowance Center for Human Immunology, Department of Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Dmitry M
authors.initials: DM
authors.lastname: Shayakhmetov
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Veterans Affairs Medical Center, Iowa City, Iowa, United States of America.
authors.forename: Fayyaz S
authors.initials: FS
authors.lastname: Sutterwala
authors.affiliation: Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.|Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Cassel
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D005620:Freund's Adjuvant; D007114:Immunization; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D051379:Mice; D010047:Ovalbumin; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D058847:Inflammasomes; D053582:Interleukin-1alpha; D010047:Ovalbumin; D005620:Freund's Adjuvant