IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages

Hui-Rong Jiang, Marija Milovanović, Debbie Allan, Wanda Niedbala, Anne-Galle Besnard, Sandra Y Fukada, Jose C Alves-Filho, Dieudonnée Togbe, Carl S Goodyear, Christopher Linington, Damo Xu, Miodrag L Lukic, Foo Y Liew

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Abstract

Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2(-/-) EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-γ but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR(+) PD-L2(+) cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.
LanguageEnglish
Pages1804–1814
Number of pages11
JournalEuropean Journal of Immunology
Volume42
Issue number7
Early online date12 Jun 2012
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Autoimmune Experimental Encephalomyelitis
Interleukin-17
Macrophages
Autoimmune Diseases of the Nervous System
Central Nervous System Diseases
Spinal Cord
Interleukin-13
Adoptive Transfer
Interleukins
Immune System Diseases
Interleukin-5
Interleukin-33
Interleukin-1
Immune System
Anti-Inflammatory Agents
Central Nervous System
Lymph Nodes
Cytokines
Phenotype

Keywords

  • experimental autoimmune encephalomyelitis
  • IL-33
  • M2 macrophages
  • Th17/Th1

Cite this

Jiang, Hui-Rong ; Milovanović, Marija ; Allan, Debbie ; Niedbala, Wanda ; Besnard, Anne-Galle ; Fukada, Sandra Y ; Alves-Filho, Jose C ; Togbe, Dieudonnée ; Goodyear, Carl S ; Linington, Christopher ; Xu, Damo ; Lukic, Miodrag L ; Liew, Foo Y. / IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages. In: European Journal of Immunology. 2012 ; Vol. 42, No. 7. pp. 1804–1814.
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title = "IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages",
abstract = "Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2(-/-) EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-γ but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR(+) PD-L2(+) cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.",
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author = "Hui-Rong Jiang and Marija Milovanović and Debbie Allan and Wanda Niedbala and Anne-Galle Besnard and Fukada, {Sandra Y} and Alves-Filho, {Jose C} and Dieudonn{\'e}e Togbe and Goodyear, {Carl S} and Christopher Linington and Damo Xu and Lukic, {Miodrag L} and Liew, {Foo Y}",
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Jiang, H-R, Milovanović, M, Allan, D, Niedbala, W, Besnard, A-G, Fukada, SY, Alves-Filho, JC, Togbe, D, Goodyear, CS, Linington, C, Xu, D, Lukic, ML & Liew, FY 2012, 'IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages' European Journal of Immunology, vol. 42, no. 7, pp. 1804–1814. https://doi.org/10.1002/eji.201141947

IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages. / Jiang, Hui-Rong; Milovanović, Marija; Allan, Debbie; Niedbala, Wanda; Besnard, Anne-Galle; Fukada, Sandra Y; Alves-Filho, Jose C; Togbe, Dieudonnée; Goodyear, Carl S; Linington, Christopher; Xu, Damo; Lukic, Miodrag L; Liew, Foo Y.

In: European Journal of Immunology, Vol. 42, No. 7, 07.2012, p. 1804–1814.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages

AU - Jiang, Hui-Rong

AU - Milovanović, Marija

AU - Allan, Debbie

AU - Niedbala, Wanda

AU - Besnard, Anne-Galle

AU - Fukada, Sandra Y

AU - Alves-Filho, Jose C

AU - Togbe, Dieudonnée

AU - Goodyear, Carl S

AU - Linington, Christopher

AU - Xu, Damo

AU - Lukic, Miodrag L

AU - Liew, Foo Y

N1 - © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2012/7

Y1 - 2012/7

N2 - Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2(-/-) EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-γ but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR(+) PD-L2(+) cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.

AB - Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2(-/-) EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-γ but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR(+) PD-L2(+) cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.

KW - experimental autoimmune encephalomyelitis

KW - IL-33

KW - M2 macrophages

KW - Th17/Th1

U2 - 10.1002/eji.201141947

DO - 10.1002/eji.201141947

M3 - Article

VL - 42

SP - 1804

EP - 1814

JO - European Journal of Immunology

T2 - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

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