IL-33 amplifies an innate immune response in the degenerating retina

Xi, Hongkang; Katschke, Kenneth J.; Li, Yun; Truong, Tom; Lee, Wyne P.; Diehl, Lauri; Rangell, Linda; Tao, Jianhua; Arceo, Rommel; Eastham-Anderson, Jeffrey; Hackney, Jason A.; Iglesias, Antonio; Cote-Sierra, Javier; Elstrott, Justin; Weimer, Robby M.; Campagne, Menno van Lookeren

doi:10.1084/jem.20150894

Cited by 75 publications

(103 citation statements)

References 52 publications

(72 reference statements)

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“…IL-33 is unique as it is active without caspase-1 cleavage and does not require inflammasome activation for secretion and bioactivity. 109 IL-33 triggers an inflammatory response, recruiting monocytes, contributing to photoreceptor loss in a photoxic retinal model of degeneration 110 and infers a pathogenic role of endogenous IL-33 and an a priori for neutralising IL-33 to reduce myeloid cell accumulation as a possible intervention. However, as with IL-18, and in consideration of the emerging role of IL-33 in inflammatory disorders 111,112 and in the absence of progressive cell death, IL-33 regulates tissue responses.…”

Section: Macrophage Conditioning Angiogenesis and Tissue Viabilitymentioning

confidence: 97%

Doyne lecture 2016: intraocular health and the many faces of inflammation

Dick

2016

Eye

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Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses.

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Section: Macrophage Conditioning Angiogenesis and Tissue Viabilitymentioning

confidence: 97%

Doyne lecture 2016: intraocular health and the many faces of inflammation

Dick

2016

Eye

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“…(Hudson et al, 2008). Further studies have confirmed that IL-33 is a critical inducer of chemokines in various CNS injury models (Gadani et al, 2015b;Xi et al, 2016), and it is likely affecting both astrocytes and microglia (Gadani et al, 2015b). By RT-PCR ST2 mRNA is highest on microglia at baseline, but interestingly is downregulated by microglia and upregulated by astrocytes after injury (Gadani et al, 2015b).…”

Section: Cellular Expression and Effector Functions Of Il-33 In The Cnsmentioning

confidence: 89%

“…Another recent study addressed IL-33 expression in the retina, finding it expressed in both mouse and human vimentin + Müller glia (Xi et al, 2016). In analysis of retinas from human macular degeneration patients, they also demonstrated upregulation in the diseased tissue relative to healthy controls (Xi et al, 2016).…”

Section: Cellular Expression and Effector Functions Of Il-33 In The Cnsmentioning

confidence: 99%

“…Studies exist regarding IL-33 in other CNS conditions, including stroke Luo et al, 2015), neuropathic pain (Zarpelon et al, 2016;Liu et al, 2015), infection (Peng et al, 2013;Hudson et al, 2008;Palomo et al, 2015;Tong and Lu, 2015), and age related macular degeneration (Xi et al, 2016), but given a dearth of literature these will not be specifically discussed here.…”

Section: Il-33 In Cns Pathologymentioning

confidence: 99%

“…In theory any necrotic death of oligodendrocytes or IL-33 + astrocytes will result in IL-33 release, but there are several reports of IL-33 release in the absence of cell death (Xi et al, 2016;Fock et al, 2013;Kakkar et al, 2012). One example of this is in retinal chronic light exposure injury.…”

Section: Il-33 In Cns Injurymentioning

confidence: 99%

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Interleukin 33 Initiates CNS Inflammation Following Traumatic Injury

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Current perspectives on the interleukin‐1 family as targets for inflammatory disease

et al. 2019

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Since the first description of interleukin-1 (IL-1) and the genesis of the field of cytokine biology, the understanding of how IL-1 and related cytokines play central orchestrating roles in the inflammatory response has been an area of intense investigation. As a consequence of these endeavours, specific strategies have been developed to target the function of the IL-1 family in human disease realizing significant impacts for patients. While the most significant advances to date have been associated with inhibition of the prototypical family members IL-1α/β, approaches to target more recently identified family members such as IL-18, IL-33 and the IL-36 subfamily are now beginning to come to fruition. This review summarizes current knowledge surrounding the roles of the IL-1 family in human disease and describes the rationale and strategies which have been developed to target these cytokines to inhibit the pathogenesis of a wide range of diseases in which inflammation plays a centrally important role.Keywords: Canakinumab r Inflammation r Inflammatory disease r Interleukin-1 family r Therapy

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IL-33 amplifies an innate immune response in the degenerating retina

Abstract: Xi et al. demonstrate that IL-33 is a key regulator of retinal inflammation and degeneration.

Cited by 75 publications

References 52 publications

Doyne lecture 2016: intraocular health and the many faces of inflammation

Doyne lecture 2016: intraocular health and the many faces of inflammation

Interleukin 33 Initiates CNS Inflammation Following Traumatic Injury

Current perspectives on the interleukin‐1 family as targets for inflammatory disease

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