Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development
The IL-36 subfamily of cytokines belongs to the IL-1 superfamily and consists of three pro-inflammatory agonists IL-36α, IL-36β, IL-36γ, and an IL-36 receptor (IL-36R) antagonist, IL-36Ra. These IL-36 cytokines function through a common receptor to modulate innate and adaptive immune responses. IL-3...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00317/full |
| _version_ | 1818325400561909760 |
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| author | Dawn Queen Chathumadavi Ediriweera Liang Liu |
| author_facet | Dawn Queen Chathumadavi Ediriweera Liang Liu |
| author_sort | Dawn Queen |
| collection | DOAJ |
| description | The IL-36 subfamily of cytokines belongs to the IL-1 superfamily and consists of three pro-inflammatory agonists IL-36α, IL-36β, IL-36γ, and an IL-36 receptor (IL-36R) antagonist, IL-36Ra. These IL-36 cytokines function through a common receptor to modulate innate and adaptive immune responses. IL-36 cytokines are expressed as inactive precursors and require proteolytic processing to become fully active. Upon binding to IL-36R, IL-36 agonists augment the expression and production of inflammatory cytokines via activating signaling pathways. IL-36 is mainly expressed in epidermal, bronchial, and intestinal epithelial cells that form the barrier structures of the body and regulates the balance between pro-inflammatory and anti-inflammatory cytokine production at these tissue sites. Dysregulation of IL-36 signaling is a major etiological factor in the development of autoimmune and inflammatory diseases. Besides its critical role in inflammatory skin diseases such as psoriasis, emerging evidence suggests that aberrant IL-36 activities also promote inflammatory diseases in the lung, kidneys, and intestines, underscoring the potential of IL-36 as a therapeutic target for common inflammatory diseases. The role of IL-36 signaling in cancer development is also under investigation, with limited studies suggesting a potential anti-tumor effect. In this comprehensive review, we summarize current knowledge regarding the expression, activation, regulatory mechanisms, and biological functions of IL-36 signaling in immunity, inflammatory diseases, and cancer development. |
| first_indexed | 2024-12-13T11:43:53Z |
| format | Article |
| id | doaj.art-dab1d51f24304537a9f0bee51c6b713f |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T11:43:53Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-dab1d51f24304537a9f0bee51c6b713f2022-12-21T23:47:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-12-01710.3389/fcell.2019.00317496193Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer DevelopmentDawn Queen0Chathumadavi Ediriweera1Liang Liu2Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United StatesThe Hormel Institute, University of Minnesota, Austin, MN, United StatesThe Hormel Institute, University of Minnesota, Austin, MN, United StatesThe IL-36 subfamily of cytokines belongs to the IL-1 superfamily and consists of three pro-inflammatory agonists IL-36α, IL-36β, IL-36γ, and an IL-36 receptor (IL-36R) antagonist, IL-36Ra. These IL-36 cytokines function through a common receptor to modulate innate and adaptive immune responses. IL-36 cytokines are expressed as inactive precursors and require proteolytic processing to become fully active. Upon binding to IL-36R, IL-36 agonists augment the expression and production of inflammatory cytokines via activating signaling pathways. IL-36 is mainly expressed in epidermal, bronchial, and intestinal epithelial cells that form the barrier structures of the body and regulates the balance between pro-inflammatory and anti-inflammatory cytokine production at these tissue sites. Dysregulation of IL-36 signaling is a major etiological factor in the development of autoimmune and inflammatory diseases. Besides its critical role in inflammatory skin diseases such as psoriasis, emerging evidence suggests that aberrant IL-36 activities also promote inflammatory diseases in the lung, kidneys, and intestines, underscoring the potential of IL-36 as a therapeutic target for common inflammatory diseases. The role of IL-36 signaling in cancer development is also under investigation, with limited studies suggesting a potential anti-tumor effect. In this comprehensive review, we summarize current knowledge regarding the expression, activation, regulatory mechanisms, and biological functions of IL-36 signaling in immunity, inflammatory diseases, and cancer development.https://www.frontiersin.org/article/10.3389/fcell.2019.00317/fullIL-36 signalinginflammationcytokinepsoriasiscancer |
| spellingShingle | Dawn Queen Chathumadavi Ediriweera Liang Liu Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development Frontiers in Cell and Developmental Biology IL-36 signaling inflammation cytokine psoriasis cancer |
| title | Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development |
| title_full | Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development |
| title_fullStr | Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development |
| title_full_unstemmed | Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development |
| title_short | Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development |
| title_sort | function and regulation of il 36 signaling in inflammatory diseases and cancer development |
| topic | IL-36 signaling inflammation cytokine psoriasis cancer |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00317/full |
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