Immune complexes indirectly suppress the generation of Th17 Responses In Vivo

Ceren Ciraci; John R. Janczy; Nidhi Jain; Stefanie Haasken; Cyntia Pecli E Silva; Claudia F. Benjamim; Jeffrey J. Sadler; Alicia K. Olivier; Yoichiro Iwakura; Dmitry M. Shayakhmetov; Fayyaz S. Sutterwala; Suzanne L. Cassel

doi:10.1371/journal.pone.0151252

Immune complexes indirectly suppress the generation of Th17 Responses In Vivo

Ceren Ciraci, John R. Janczy, Nidhi Jain, Stefanie Haasken, Cyntia Pecli E Silva, Claudia F. Benjamim, Jeffrey J. Sadler, Alicia K. Olivier, Yoichiro Iwakura, Dmitry M. Shayakhmetov, Fayyaz S. Sutterwala, Suzanne L. Cassel

Department of Molecular Biology and Genetics

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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.

Original language	English
Article number	e0151252
Journal	PLoS ONE
Volume	11
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0151252
Publication status	Published - Mar 2016

Bibliographical note

Publisher Copyright:
© 2016 Ciraci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

Funders	Funder number
National Institute of Allergy and Infectious Diseases	R01AI104706

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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 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.",

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AU - Janczy, John R.

AU - Jain, Nidhi

AU - Haasken, Stefanie

AU - E Silva, Cyntia Pecli

AU - Benjamim, Claudia F.

AU - Sadler, Jeffrey J.

AU - Olivier, Alicia K.

AU - Iwakura, Yoichiro

AU - Shayakhmetov, Dmitry M.

AU - Sutterwala, Fayyaz S.

AU - Cassel, Suzanne L.

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N2 - 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.

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Immune complexes indirectly suppress the generation of Th17 Responses In Vivo

Abstract

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