Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation

Cohen, E. Suzanne; Scott, Ian; Majithiya, Jayesh B.; Rapley, Laura; Kemp, Benjamin; England, Elizabeth; Rees, Dianne; Overed-Sayer, Catherine; Woods, Jennifer; Bond, Nicholas J.; Veyssier, Christel Séguy; Embrey, Kevin J.; Sims, Dorothy A.; Snaith, Michael; Vousden, Katherine A.; Strain, Martin; Chan, Denice T. Y.; Carmen, Sara; Huntington, Catherine E. Chaillan; Flavell, Liz; Xu, Jianqing; Popović, Bojana; Brightling, Christopher E.; Vaughan, Tristan J.; Butler, Robin; Lowe, David C.; Higazi, Daniel R.; Corkill, Dominic J.; May, Richard; Sleeman, Matthew A.; Mustelin, Tomas

doi:10.1038/ncomms9327

Cited by 216 publications

(282 citation statements)

References 41 publications

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“…EC-SOD's attenuation of the IL-33 response was notable, given the key role of IL-33 in asthma and the importance of IL-33 in the activation of ILC2s. IL-33 regulates ST2-dependent activation in ILC2s (29,39) and oxidative radicals affect IL-33 disulphide bond formation (39), indicating that oxidative stress might have a direct impact on the IL-33-dependent activation of ST2 in ILC2s. ILC2s play a major role in the pathogenesis of allergic diseases such as atopic dermatitis and asthma (40) by secreting massive amounts of IL-5, IL-9, and IL-13 (31).…”

Section: Discussionmentioning

confidence: 99%

The R213G polymorphism in SOD3 protects against allergic airway inflammation

Gaurav¹,

Varasteh²,

Weaver³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

The R213G polymorphism in SOD3 protects against allergic airway inflammation

Gaurav¹,

Varasteh²,

Weaver³

et al. 2017

JCI Insight

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“…Expression and secretion of IL-33 (IL1F11) and IL-25 (IL-17E) are highly regulated in AECs [20][21][22]. Both cytokines act as amplifiers of the allergic inflammatory immune response [23,24] via the membrane receptors IL-33R and IL-17RA/IL-17RB, respectively, which are highly expressed in various immune cells, including ILC2s, MCs, basophils, DCs and macrophages [25][26][27][28][29].…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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“…After its release, IL-33 is inactivated by proteolytic cleavage 28 or oxidation. 29 IL-33 is predominantly expressed in epithelial and endothelial cells. High constitutive release generates an allergic inflammation with eosinophilia.…”

Section: Discusionmentioning

confidence: 99%

IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment

et al. 2018

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Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokine that can activate innate and adaptive immunity. We studied the effectiveness of local IL-33 delivery in the treatment of cancer that has metastasized to the peritoneal cavity. Direct peritoneal administration of IL-33 delayed the progression of metastatic peritoneal cancer. Prolongation in survival was not associated with a direct effect of IL-33 on tumor cells, but with major changes in the immune microenvironment of the tumor. IL-33 promoted a significant increase in the leukocyte compartment of the tumor immunoenvironment and an allergic cytokine profile. We observed a substantial increase in the number of activated CD4+ T-cells accompanied by peritoneal eosinophil infiltration, B-cell activation and activation of peritoneal macrophages which displayed tumoricidal capacity. Depletion of CD4+ cells, eosinophils or macrophages reduced the anti-tumor effects of IL-33 but none of these alone were sufficient to completely abrogate its positive benefit. In conclusion, local administration of IL-33 generates an allergic tumor environment resulting in a novel approach for treatment of metastatic peritoneal malignancies, such as advanced ovarian cancer.

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Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation

Cited by 216 publications

References 41 publications

The R213G polymorphism in SOD3 protects against allergic airway inflammation

The R213G polymorphism in SOD3 protects against allergic airway inflammation

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment

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