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IL-33 attenuates the development of experimental autoimmune uveitis

Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (S...

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Autores principales: Barbour, Mark, Allan, Debbie, Xu, Heping, Pei, Cheng, Chen, Mei, Niedbala, Wanda, Fukada, Sandra Y, Besnard, Anne-Galle, Alves-Filho, Jose C, Tong, Xiaoguang, Forrester, John V, Liew, Foo Yew, Jiang, Hui-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449115/
https://www.ncbi.nlm.nih.gov/pubmed/25116404
http://dx.doi.org/10.1002/eji.201444671
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author Barbour, Mark
Allan, Debbie
Xu, Heping
Pei, Cheng
Chen, Mei
Niedbala, Wanda
Fukada, Sandra Y
Besnard, Anne-Galle
Alves-Filho, Jose C
Tong, Xiaoguang
Forrester, John V
Liew, Foo Yew
Jiang, Hui-Rong
author_facet Barbour, Mark
Allan, Debbie
Xu, Heping
Pei, Cheng
Chen, Mei
Niedbala, Wanda
Fukada, Sandra Y
Besnard, Anne-Galle
Alves-Filho, Jose C
Tong, Xiaoguang
Forrester, John V
Liew, Foo Yew
Jiang, Hui-Rong
author_sort Barbour, Mark
collection PubMed
description Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ(+) and IL-17(+) CD4(+) T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis.
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spelling pubmed-44491152015-06-04 IL-33 attenuates the development of experimental autoimmune uveitis Barbour, Mark Allan, Debbie Xu, Heping Pei, Cheng Chen, Mei Niedbala, Wanda Fukada, Sandra Y Besnard, Anne-Galle Alves-Filho, Jose C Tong, Xiaoguang Forrester, John V Liew, Foo Yew Jiang, Hui-Rong Eur J Immunol Immunomodulation Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ(+) and IL-17(+) CD4(+) T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis. BlackWell Publishing Ltd 2014-11 2014-10-18 /pmc/articles/PMC4449115/ /pubmed/25116404 http://dx.doi.org/10.1002/eji.201444671 Text en © 2014 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Immunomodulation
Barbour, Mark
Allan, Debbie
Xu, Heping
Pei, Cheng
Chen, Mei
Niedbala, Wanda
Fukada, Sandra Y
Besnard, Anne-Galle
Alves-Filho, Jose C
Tong, Xiaoguang
Forrester, John V
Liew, Foo Yew
Jiang, Hui-Rong
IL-33 attenuates the development of experimental autoimmune uveitis
title IL-33 attenuates the development of experimental autoimmune uveitis
title_full IL-33 attenuates the development of experimental autoimmune uveitis
title_fullStr IL-33 attenuates the development of experimental autoimmune uveitis
title_full_unstemmed IL-33 attenuates the development of experimental autoimmune uveitis
title_short IL-33 attenuates the development of experimental autoimmune uveitis
title_sort il-33 attenuates the development of experimental autoimmune uveitis
topic Immunomodulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449115/
https://www.ncbi.nlm.nih.gov/pubmed/25116404
http://dx.doi.org/10.1002/eji.201444671
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