The IL-1-Like Cytokine IL-33 Is Constitutively Expressed in the Nucleus of Endothelial Cells and Epithelial Cells In Vivo: A Novel ‘Alarmin’?
By C. Moussion, N. Ortéga, J. Girard. PLoS ONE, 2008
1,186 citations recorded by the source corpus.
Background Interleukin-33 (IL-33) is an IL-1-like cytokine ligand for the IL-1 receptor-related protein ST2, that activates mast cells and Th2 lymphocytes, and induces production of Th2-associated cytokines in vivo. We initially discovered IL-33 as a nuclear factor (NF-HEV) abundantly expressed in high endothelial venules from lymphoid organs, that associates with chromatin and exhibits transcriptional regulatory properties. This suggested that, similarly to IL-1α and chromatin-associated cytokine HMGB1, IL-33 may act as both a cytokine and a nuclear factor. Although the activity of recombinant IL-33 has been well characterized, little is known yet about the expression pattern of endogenous IL-33 in vivo. Methodology/Principal Findings Here, we show that IL-33 is constitutively and abundantly expressed in normal human tissues. Using a combination of human tissue microarrays and IL-33 monoclonal and polyclonal antibodies, we found that IL-33 is a novel nuclear marker of the endothelium widely expressed along the vascular tree. We observed abundant nuclear expression of IL-33 in endothelial cells from both large and small blood vessels in most normal human tissues, as well as in human tumors. In addition to endothelium, we also found constitutive nuclear expression of IL-33 in fibroblastic reticular cells of lymphoid tissues, and epithelial cells of tissues exposed to the environment, including skin keratinocytes and epithelial cells of the stomach, tonsillar crypts and salivary glands. Conclusions/Significance Together, our results indicate that, unlike inducible cytokines, IL-33 is constitutively expressed in normal human tissues. In addition, they reveal that endothelial cells and epithelial cells constitute major sources of IL-33 in vivo. Based on these findings, we speculate that IL-33 may function, similarly to the prototype ‘alarmin’ HMGB1, as an endogenous ‘danger’ signal to alert the immune system after endothelial or epithelial cell damage during trauma or infection.
Subfields: Dermatology, Immunology, Surgery
View Paper: https://www.semanticscholar.org/paper/669ab65d1832d1aacd1aed010de55b12f69cfab7
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Citations in the corpus
- IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. (2014, background): “IL-33 was thus proposed to function as a novel alarmin (intracellular alarm signal released upon cell injury) to alert the immune system of tissue damage following trauma or infection [36,37 ,45,46].”
- Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. (2012, background): “IL-33 is known to be constitutively expressed in endothelial and epithelial cells and is released as an alarmin upon cell damage (Moussion et al., 2008).”
- IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation1 (2009, background): “IL-33 is released by endothelial or epithelial cell damage during trauma or infection (9, 43).”
- Decoding cell death signals in liver inflammation. (2013, background): “Furthermore, the circulating levels of IL-33 are elevated in patients 3 vol. 59 j 583–594 589 Fig.”
- Disease-associated functions of IL-33: the new kid in the IL-1 family (2010, background): “At the protein level, IL-33 is mainly expressed by fibroblast”
- The sterile inflammatory response (2010, background): “There are also other IL-1-related cytokine genes that utilize other receptors (e.g. IL-18, IL-33), but there are as of yet few studies to investigate whether they are involved in the sterile inflammatory response (41, 62, 63).”