Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice

Chen, H; Sun, Yun; Lai, Lin; Wu, Hongxu; Xiao, Yunfeng; Ming, Bingxia; Gao, Ming; Zou, Huijuan; Xiong, Ping; Xu, Yu; Tan, Zheng; Gong, Feili; Zheng, Fang

doi:10.1016/j.neuroscience.2015.09.019

Cited by 49 publications

(48 citation statements)

References 47 publications

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“…IL-33 is an unconventional cytokine because it has a proinflammatory face related to its alarmin function, but it can also suppress inflammation in some clinical settings by driving type 2 immunity. This activity is illustrated by the protective role of IL-33 in hepatitis (6), colitis (7), experimental autoimmune encephalomyelitis (8,9), uveitis (10), and atherosclerosis (11). However, a similar amplification of this type 2 immune response, initiated by IL-33, aggravates asthma, which is clearly a Th2-driven disease (12).…”

mentioning

confidence: 99%

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

Biton

Athari

Thiolat

et al. 2016

The Journal of Immunology

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IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33–treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33–treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39high Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development.

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confidence: 99%

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

Biton

Athari

Thiolat

et al. 2016

The Journal of Immunology

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“…Conversely, IL-33 mediates pathogenic eosinophilic responses in Angiostrongylus cantonensis infection-induced meningitis, and antibodies against ST2 or IL-33 blockade reduce disease severity [66][67][68]. In the model of experimental autoimmune encephalomyelitis (EAE), IL-33 blockade mediates both pathogenic and protective roles [69][70][71]. Collectively, the data indicate that IL-33 likely mediates neuroprotective functions in various brain injury models.…”

Section: Central Nervous Systemmentioning

confidence: 99%

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

Chen

Tsai

Yang

et al. 2018

Cell Physiol Biochem

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Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses via interaction with its receptor, ST2. Activation of ST2 signalling by IL-33 triggers pleiotropic immune functions in multiple ST2-expressing immune cells, including macrophages, neutrophils, eosinophils, basophils, mast cells, type 2 helper T cells, regulatory T cells, and group 2 innate lymphoid cells. IL-33-mediated effector functions contribute to the tissue inflammatory and reparative responses in various organs including lung, skin, kidney, central nerve system, cardiovascular system, and gastrointestinal system. Endogenous IL-33/ ST2 signaling exhibits diverse immune regulatory functions during progression of different diseases. IL-33 likely functions as a disease sensitizer and plays pathological roles in inflamed tissues in allergic disorders that involve hyperreactive immune responses in the context of skin and pulmonary allergy. However, IL-33 also mediates tissue-protective functions during the recovery phase following tissue injury in the central nerve system and gastrointestinal system. Modulation of the IL-33/ST2 axis, therefore, represents a promising strategy for treating immune disorders that involve dysregulation of the cytokine signalling. In the past two decades, therapeutic strategies blocking IL-33/ST2 have been extensively studied for the treatment of diseases in animal models. In this review, the current progress on the development of therapeutic biologics for targeting IL-33/ST2 signalling in inflammatory diseases is summarized.

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“…In the latest research we also found that IL-33 is highly expressed in the central nervous system (CNS) (4), in which IL-33 is over 10 fold more than in liver, spleen and lung (unpublished data from our lab). IL-33 is mostly released as a damage-associated molecular pattern (DAMP) molecule from damaged cells (2,3,5) or be processed and released from activated cells (2,4,6) to the extracellular milieu and plays an important role in many indicated diseases such as inflammatory bowel disease, allergy, autoimmune disease, transplantation rejection, graft-versus-host disease (GVHD), infectious disease, and cancers (3,5,7).…”

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confidence: 99%

The emerging role of sST2 blocking in the therapy of graft-versus-host disease

Xiao

Zheng

2016

Ann. Transl. Med.

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Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice

Cited by 49 publications

References 47 publications

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis

Therapeutic Strategies for Targeting IL-33/ST2 Signalling for the Treatment of Inflammatory Diseases

The emerging role of sST2 blocking in the therapy of graft-versus-host disease

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