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Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category
Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans. We examined the role of the interleukin (IL)-23–IL-17 and IL-12–T helper cell (Th)1 pathways in the pathogenesis of EAU. IL–23 but not IL-12 was necessary to elicit disease by immunization with the retinal antigen (Ag) in...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292220/ https://www.ncbi.nlm.nih.gov/pubmed/18391061 http://dx.doi.org/10.1084/jem.20071258 |
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author | Luger, Dror Silver, Phyllis B. Tang, Jun Cua, Daniel Chen, Zoe Iwakura, Yoichiro Bowman, Edward P. Sgambellone, Nicole M. Chan, Chi-Chao Caspi, Rachel R. |
author_facet | Luger, Dror Silver, Phyllis B. Tang, Jun Cua, Daniel Chen, Zoe Iwakura, Yoichiro Bowman, Edward P. Sgambellone, Nicole M. Chan, Chi-Chao Caspi, Rachel R. |
author_sort | Luger, Dror |
collection | PubMed |
description | Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans. We examined the role of the interleukin (IL)-23–IL-17 and IL-12–T helper cell (Th)1 pathways in the pathogenesis of EAU. IL–23 but not IL-12 was necessary to elicit disease by immunization with the retinal antigen (Ag) interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. IL-17 played a dominant role in this model; its neutralization prevented or reversed disease, and Th17 effector cells induced EAU in the absence of interferon (IFN)-γ. In a transfer model, however, a polarized Th1 line could induce severe EAU independently of host IL-17. Furthermore, induction of EAU with IRBP-pulsed mature dendritic cells required generation of an IFN-γ–producing effector response, and an IL-17 response by itself was insufficient to elicit pathology. Finally, genetic deficiency of IL-17 did not abrogate EAU susceptibility. Thus, autoimmune pathology can develop in the context of either a Th17 or a Th1 effector response depending on the model. The data suggest that the dominant effector phenotype may be determined at least in part by conditions present during initial exposure to Ag, including the quality/quantity of Toll-like receptor stimulation and/or type of Ag-presenting cells. These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm. |
format | Text |
id | pubmed-2292220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22922202008-10-14 Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category Luger, Dror Silver, Phyllis B. Tang, Jun Cua, Daniel Chen, Zoe Iwakura, Yoichiro Bowman, Edward P. Sgambellone, Nicole M. Chan, Chi-Chao Caspi, Rachel R. J Exp Med Articles Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans. We examined the role of the interleukin (IL)-23–IL-17 and IL-12–T helper cell (Th)1 pathways in the pathogenesis of EAU. IL–23 but not IL-12 was necessary to elicit disease by immunization with the retinal antigen (Ag) interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. IL-17 played a dominant role in this model; its neutralization prevented or reversed disease, and Th17 effector cells induced EAU in the absence of interferon (IFN)-γ. In a transfer model, however, a polarized Th1 line could induce severe EAU independently of host IL-17. Furthermore, induction of EAU with IRBP-pulsed mature dendritic cells required generation of an IFN-γ–producing effector response, and an IL-17 response by itself was insufficient to elicit pathology. Finally, genetic deficiency of IL-17 did not abrogate EAU susceptibility. Thus, autoimmune pathology can develop in the context of either a Th17 or a Th1 effector response depending on the model. The data suggest that the dominant effector phenotype may be determined at least in part by conditions present during initial exposure to Ag, including the quality/quantity of Toll-like receptor stimulation and/or type of Ag-presenting cells. These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm. The Rockefeller University Press 2008-04-14 /pmc/articles/PMC2292220/ /pubmed/18391061 http://dx.doi.org/10.1084/jem.20071258 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Luger, Dror Silver, Phyllis B. Tang, Jun Cua, Daniel Chen, Zoe Iwakura, Yoichiro Bowman, Edward P. Sgambellone, Nicole M. Chan, Chi-Chao Caspi, Rachel R. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
title | Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
title_full | Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
title_fullStr | Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
title_full_unstemmed | Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
title_short | Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
title_sort | either a th17 or a th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292220/ https://www.ncbi.nlm.nih.gov/pubmed/18391061 http://dx.doi.org/10.1084/jem.20071258 |
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