Interleukin 33 as a Mechanically Responsive Cytokine Secreted by Living Cells

Kakkar, Rahul; Hei, Hillary; Dobner, Stephan; Lee, Richard T.

doi:10.1074/jbc.m111.298703

Cited by 258 publications

(150 citation statements)

References 20 publications

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“…However, it is unclear if cell death can account entirely for the biologic effects of IL-33. IL-33 release from living cells was reported in human bronchial epithelium exposed to Alternaria (Kouzaki et al, 2011) and from mechanically-stressed fibroblasts in vitro and in vivo (Kakkar et al, 2012). Several studies suggest extracellular ATP can promote IL-33 production or secretion in models of allergic inflammation(Byers et al, 2013; Hudson et al, 2008; Kouzaki et al, 2011).…”

Section: Il-33 Release And/or Secretionmentioning

confidence: 99%

“…Inflammatory DCs also interact with fibroblastic reticular cells (FRC), which mediate lymph node remodeling and enlargement during infection (Acton et al, 2014). HEV and FRC are primary sources of lymph node IL-33 in mice and humans (Moussion et al, 2008; Pichery et al, 2012), and release of IL-33 in these cells might reflect mechanical forces inherent in the rapid inflammation-induced changes in lymph node size, akin to findings in fibroblasts (Kakkar et al, 2012). In contrast, ILC2s, mast cells and ST2 + Tregs are rare in lymphoid tissues (Molofsky et al, 2015; Nussbaum et al, 2013), potentially limiting competition for IL-33 and allowing IL-12 to drive low amounts of ST2 expression on inflammatory lymphocytes that enables competence to detect IL-33.…”

Section: Il-33-st2 In Infection and Non-allergic Inflammationmentioning

confidence: 99%

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Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation

2015

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Summary Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks. IL-33 can participate in pathologic fibrotic reactions, or, in the setting of microbial invasion, can cooperate with inflammatory cytokines to promote responses by cytotoxic NK cells, Th1 cells and CD8+ T cells. Here, we highlight the regulation and function of IL-33 and ST2, and review their roles in homeostasis, damage and inflammation, suggesting a conceptual framework for future studies.

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Section: Il-33 Release And/or Secretionmentioning

confidence: 99%

Section: Il-33-st2 In Infection and Non-allergic Inflammationmentioning

confidence: 99%

Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation

2015

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“…For example, IL-33, a potent ILC2 activator, is constitutively maintained in the nucleus of epithelial and endothelial cells as a pro-cytokine and released during necrosis or mechanical strain [52,53]. Therefore, by monitoring IL-33, ILC2s can promote eosinophil and AAM accumulation following local tissue damage, a response that the results discussed above suggest could mitigate tissue injury.…”

Section: Ilc2s: Integrating Homeostatic Signalsmentioning

confidence: 99%

I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis

Moltke

Locksley

2014

Current Opinion in Immunology

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Innate type 2 immune cells are activated in response to helminths, allergens, and certain types of proteases and particulates. Recently, innate type 2 immune pathways have also been implicated in protective host responses to homeostatic perturbations, such as metabolic dysfunction, atherosclerosis, and tissue injury. In this context, innate type 2 cytokines stimulate local tissues, recruit eosinophils, and alternatively activate macrophages to restore homeostasis. As the major source of innate interleukin (IL)-5 and IL-13, group 2 innate lymphoid cells are positioned to initiate and maintain homeostatic type 2 responses. The absence of exogenous stimuli in these processes implicates endogenous pathways in the activation of type 2 immunity and suggests an alternative evolutionary trajectory for type 2 immunity, apart from its role in response to helminths and allergens.

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“…However, it can be speculated as the follows reasons. First, the identification of a nuclear localization sequence in IL-33 suggests that IL-33 is released from dying cells into the extracellular matrix to signal damage (Bianchi 2007) or by cells undergoing mechanical stress (Kakkar et al 2012). IL-33 may serve this purpose after SAH, which is known to induce neuronal apoptosis, necrosis, and other types of injury (Charriaut-Marlangue et al 1996;Graham and Chen 2001).…”

Section: Discussionmentioning

confidence: 99%

IL-33 Expression in the Cerebral Cortex Following Experimental Subarachnoid Hemorrhage in Rats

Huang

Sun³

et al. 2014

Cell Mol Neurobiol

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Subarachnoid hemorrhage (SAH) is a pervasive and devastating condition in which inflammatory and apoptotic pathways contribute to poor outcome. Interleukin-33 (IL-33) plays a crucial role in the inflammatory and apoptotic pathways through binding of the transmembrane ST2 receptor. This study investigated the expression and cellular localization of IL-33 in the cerebral cortex after SAH in order to clarify the role of IL-33 after SAH. Sprague-Dawley rats were randomly divided into sham and SAH groups and evaluated 2, 6, and 12 h and 1, 2, 3, and 5 days after the surgery, with SAH animals subjected to prechiasmatic cistern SAH. IL-33 expression was measured by western blot analysis, real-time PCR, immunohistochemistry, and immunofluorescence. The mRNA levels of tumor necrosis factor (TNF)-α and IL-1β were also assessed. The expression of IL-33, IL-1β, and TNF-α was markedly elevated in the SAH as compared to the sham group; IL-33 was mainly localized in neurons and astrocytes and not microglia after SAH. Moreover, a significant positive association was observed between IL-33 and IL-1β expression. These findings indicate that IL-33 might play an important role in the inflammatory response following SAH.

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Interleukin 33 as a Mechanically Responsive Cytokine Secreted by Living Cells

Cited by 258 publications

References 20 publications

Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation

Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation

I-L-C-2 it: type 2 immunity and group 2 innate lymphoid cells in homeostasis

IL-33 Expression in the Cerebral Cortex Following Experimental Subarachnoid Hemorrhage in Rats

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