Immune Complexes Indirectly Suppress the Generation of Th17 Responses In Vivo

• Type of Material: Article
• Authors: Ceren Ciraci, University of Iowa; John R. Janczy, University of Iowa; Nidhi Jain, University of Iowa; Stefanie Haasken, University of Iowa; Cyntia Pecli e Silva, University of Iowa; Claudia F. Benjamim, Universidade Federal do Rio de Janeiro; Jeffrey J. Sadler, University of Iowa; Alicia K. Olivier, University of Iowa; Yoichiro Iwakura, Tokyo University of Science; Dmitry Shayakhmetov, Emory University; Fayyaz S. Sutterwala, University of Iowa; Suzanne L. Cassel, University of Iowa
• Language: English
• Date: 2016-03-15
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Ciraci et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0151252
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 3
• Start Page: e0151252
• End Page: e0151252
• Grant/Funding Information: This work was supported by National Institutes of Health grants R01 AI104706 (S.L.C.), T32 AI007485 (J.R.J.), and T32 AI007511 (S.H.); an Asthma and Allergy Foundation of America fellowship (S.L.C.); an American Lung Association/The American Academy of Allergy, Asthma & Immunology Foundation Allergic Respiratory Disease Award (S.L.C.); and a Bolsista da CAPES Scholarship, 2790-14-9 (C.P.S.).
• Keywords: Cytokines; Immune suppression; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; Multidisciplinary Sciences; ADAPTIVE IMMUNITY; DENDRITIC CELLS; RECEPTOR; NLRP3 INFLAMMASOME; CD4(+) T-CELLS; Inflammation; Immune complex; Enzyme-linked immunoassays; AIRWAY INFLAMMATION; Science & Technology - Other Topics; MACROPHAGES; T cells; Dendritic cells; MICE DEFICIENT; Science & Technology; CASPASE-1; Immune response
• Research Categories: Health Sciences, Immunology; Health Sciences, General

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 ofthat 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-1 a but independent of NLRP3 inflammasome activation. Together these data represent a novel mechanism by which the generation of Th17 responses is regulated.