The Alarmin IL-33 Is a Notch Target in Quiescent Endothelial Cells

Sundlisæter, Eirik; Edelmann, Reidunn J.; Hol, Johanna; Sponheim, Jon; Küchler, Axel M.; Weiss, Miriam; Udalova, Irina A.; Midwood, Kim S.; Kasprzycka, Monika; Haraldsen, Guttorm

doi:10.1016/j.ajpath.2012.06.003

Cited by 61 publications

(50 citation statements)

References 43 publications

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“…Cellular quiescence is defined as a nonproliferating, resting state of confluent cells that is reversible after a proliferative stimulus. The nuclear localization of IL-33 is a marker of EC quiescence and is rapidly lost upon an angiogenic stimulus (59). SPARCL1 expression in primary ECs was induced when the cells reached the confluent nonproliferating state associated with the expression of nuclear IL-33 and was fully reversible after the cells were subjected to nonconfluent conditions.…”

Section: Discussionmentioning

confidence: 99%

Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma

Naschberger¹,

Liebl²,

Schellerer³

et al. 2016

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma

Naschberger¹,

Liebl²,

Schellerer³

et al. 2016

Journal of Clinical Investigation

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“…Conversely, it is also generally accepted that airway basal cells are linked to progenitor function in human lungs (36,41); here, we confirmed this proposal and established a further connection to regulated IL-33 expression and release in human lung disease. Since IL-33 expression did not fully coincide with that of other basal cell markers, the IL-33-expressing basal cells (as well as the IL-33 + serous cells in mice) appear to represent a special-endothelial cells (69), but whether this system is involved in IL-33 expression in airway epithelial cells or has any role in inflammatory lung disease still needs to be defined.…”

Section: Discussionmentioning

confidence: 99%

Long-term IL-33–producing epithelial progenitor cells in chronic obstructive lung disease

Byers

Alexander‐Brett²,

Patel³

et al. 2013

J. Clin. Invest.

272

255

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Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus infection in mice revealed an unexpected role for innate immune cells in IL-13-dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production.

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“…In contrast to humans, mouse endothelial expression of IL-33 appears restricted to adipose tissue, liver and female reproductive tract (Carlock et al, 2014; Marvie et al, 2010; Pichery et al, 2012). IL-33 expression in endothelial cells in vitro has been linked to cellular quiescence and confluence, and may require Notch signals (Küchler et al, 2008; Sundlisaeter et al, 2012). Human and mouse share constitutive IL-33 expression at epithelial surfaces, including in skin, stomach, intestine, salivary gland, vagina and lung, where expression is particularly high in alveolar type 2 cells (Mohapatra et al, 2015; Moussion et al, 2008; Pastorelli et al, 2010; Schmitz et al, 2005); species-specific differences may exist (Sundnes et al, 2015).…”

Section: Sources and Production Of Il-33mentioning

confidence: 99%

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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The Alarmin IL-33 Is a Notch Target in Quiescent Endothelial Cells

Cited by 61 publications

References 43 publications

Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma

Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma

Long-term IL-33–producing epithelial progenitor cells in chronic obstructive lung disease

Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation

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