IL-33 attenuates the development of experimental autoimmune uveitis

Mark Barbour, Debbie Allan, Heping Xu, Cheng Pei, Mei Chen, Wanda Niedbala, Sandra Y Fukada, Anne-Galle Besnard, Jose C Alves-Filho, Xiaoguang Tong, John V Forrester, Foo Yew Liew, Hui-Rong Jiang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages3320-3329
Number of pages10
JournalEuropean Journal of Immunology
Volume44
Issue number11
Early online date18 Oct 2014
DOIs
Publication statusPublished - 14 Nov 2014

Fingerprint

Uveitis
Retinal Pigments
Interleukin-17
Interleukin-5
Epithelial Cells
Macrophages
T-Lymphocytes
Eye Diseases
Interleukin-33
Immune System Diseases
Interleukin-4
Retina
Spleen
Cell Culture Techniques
Lymph Nodes
Phenotype
Messenger RNA

Keywords

  • animals
  • autoimmune diseases
  • CD4-positive T-lymphocytes
  • cultured cells
  • coculture techniques
  • disease models, animal
  • eye
  • eye proteins
  • inflammation
  • interferon-gamma
  • interleukin-17
  • interleukin-4
  • interleukin-5
  • interleukins
  • macrophages
  • mice
  • mice, inbred BALB C
  • mice, inbred C57BL
  • mice, knockout
  • RNA, messenger
  • interleukin receptors
  • retinal pigment epithelium
  • uveitis

Cite this

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. In: European Journal of Immunology. 2014 ; Vol. 44, No. 11. pp. 3320-3329.
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abstract = "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 na{\"i}ve 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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author = "Mark Barbour and Debbie Allan and Heping Xu and Cheng Pei and Mei Chen and Wanda Niedbala and Fukada, {Sandra Y} and Anne-Galle Besnard and Alves-Filho, {Jose C} and Xiaoguang Tong and Forrester, {John V} and Liew, {Foo Yew} and Hui-Rong Jiang",
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Barbour, M, Allan, D, Xu, H, Pei, C, Chen, M, Niedbala, W, Fukada, SY, Besnard, A-G, Alves-Filho, JC, Tong, X, Forrester, JV, Liew, FY & Jiang, H-R 2014, 'IL-33 attenuates the development of experimental autoimmune uveitis' European Journal of Immunology, vol. 44, no. 11, pp. 3320-3329. https://doi.org/10.1002/eji.201444671

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.

In: European Journal of Immunology, Vol. 44, No. 11, 14.11.2014, p. 3320-3329.

Research output: Contribution to journalArticle

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T1 - IL-33 attenuates the development of experimental autoimmune uveitis

AU - Barbour, Mark

AU - Allan, Debbie

AU - Xu, Heping

AU - Pei, Cheng

AU - Chen, Mei

AU - Niedbala, Wanda

AU - Fukada, Sandra Y

AU - Besnard, Anne-Galle

AU - Alves-Filho, Jose C

AU - Tong, Xiaoguang

AU - Forrester, John V

AU - Liew, Foo Yew

AU - Jiang, Hui-Rong

N1 - © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2014/11/14

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N2 - 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.

AB - 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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KW - autoimmune diseases

KW - CD4-positive T-lymphocytes

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KW - coculture techniques

KW - disease models, animal

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KW - eye proteins

KW - inflammation

KW - interferon-gamma

KW - interleukin-17

KW - interleukin-4

KW - interleukin-5

KW - interleukins

KW - macrophages

KW - mice

KW - mice, inbred BALB C

KW - mice, inbred C57BL

KW - mice, knockout

KW - RNA, messenger

KW - interleukin receptors

KW - retinal pigment epithelium

KW - uveitis

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DO - 10.1002/eji.201444671

M3 - Article

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EP - 3329

JO - European Journal of Immunology

T2 - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

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