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  4. IL-36 family cytokines in protective versus destructive inflammation
 
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2020
Journal Article
Title

IL-36 family cytokines in protective versus destructive inflammation

Abstract
The IL-1 family of cytokines and receptors are critical regulators of inflammation. Within the IL-1 family and in contrast to its IL-1 and IL-18 subfamilies, the IL-36 subfamily is still poorly characterized. Three pro-inflammatory agonists IL-36a, IL-36v, IL-36g, one IL-36 receptor (IL-1R6) antagonist, IL-36RA, and one putative IL-1R6 antagonist, IL-38, have been grouped into the IL-36 cytokine subfamily. IL-36 agonists signal through a common receptor complex to serve as early triggers of inflammatory responses by activating and cross-regulating a number of inflammatory pathways including NF-kB, MAPK and IFN signaling. IL-36RA binds to IL-1R6 to limit inflammatory signaling, while IL-38 may be an antagonist of more than one IL-1 family receptor. Expression patterns of IL-36 family cytokines, being most prominently expressed in epithelial barrier tissues such as the skin and intestines as well as in immune cells, suggest a role in protecting these barriers from infection. Dysregulation of IL-36 family cytokine signaling at physiological barriers, most prominently the skin, induces autoimmune inflammation. However, transferring the potential of IL-36 to induce tissue damage to tumors might benefit cancer patients. Here we summarize signaling pathways regulated by IL-36 family cytokines, including IL-38, and the consequences for physiological protective and pathophysiological destructive inflammation. Moreover, we discuss the limits of current knowledge on IL-36 family function to open potential avenues for research in the future.
Author(s)
Han, Y.
Huard, A.
Mora, J.
da Silva, P.
Brüne, B.
Weigert, A.
Journal
Cellular signalling  
DOI
10.1016/j.cellsig.2020.109773
Language
English
Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie IME  
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