Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
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
_version_ 1782152487229194240
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
work_keys_str_mv AT lugerdror eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT silverphyllisb eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT tangjun eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT cuadaniel eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT chenzoe eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT iwakurayoichiro eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT bowmanedwardp eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT sgambellonenicolem eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT chanchichao eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory
AT caspirachelr eitherath17orath1effectorresponsecandriveautoimmunityconditionsofdiseaseinductionaffectdominanteffectorcategory