IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential
Interleukin-33 (IL-33) is a nuclear factor and member of the IL-1 cytokine family. IL-33 is mainly expressed by epithelial and endothelial cells and exerts its function through interaction with various immune cells, and binding to its receptor can form the IL-33/Suppression of tumorigenicity 2 (ST2)...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1533335/full |
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| author | Feiya Sheng Mi Li Jia-Mei Yu Si-Yu Yang Liang Zou Guan-Jun Yang Le-Le Zhang Le-Le Zhang |
| author_facet | Feiya Sheng Mi Li Jia-Mei Yu Si-Yu Yang Liang Zou Guan-Jun Yang Le-Le Zhang Le-Le Zhang |
| author_sort | Feiya Sheng |
| collection | DOAJ |
| description | Interleukin-33 (IL-33) is a nuclear factor and member of the IL-1 cytokine family. IL-33 is mainly expressed by epithelial and endothelial cells and exerts its function through interaction with various immune cells, and binding to its receptor can form the IL-33/Suppression of tumorigenicity 2 (ST2) signaling pathway. While most cytokines are actively synthesized within cells, IL-33 is produced passively in response to tissue damage or cell necrosis, indicating its role as a signaling molecule following cellular infection, stress, or trauma. IL-33/ST2 signaling pathway has been proved to play diverse role in the pathological process of central nervous system disorders, cancer, fibrosis, autoimmune diseases, etc. Although research on the IL-33/ST2 signaling pathway has deepened recently, relevant treatment strategies have been proposed, and even targeted drugs are in the preclinical stage; further research on the effect of the IL-33/ST2 signaling pathway in different diseases is still necessary, to provide a clearer understanding of the different roles of IL-33/ST2 in disease progression and to develop new drugs and treatment strategies. Because IL-33/ST2 plays an important role in the occurrence and progression of diseases, the study of therapeutic drugs targeting this pathway is also necessary. This review focused on recent studies on the positive or negative role of IL-33/ST2 in different diseases, as well as the current related drugs targeting IL-33/ST2 in the preclinical and clinical stage. The mechanism of IL-33/ST2 in different diseases and its mediating effect on different immune cells have been summarized, as well as the antibody drugs targeting IL-33 or ST2, natural compounds with a mediating effect, and small molecule substances targeting relative pathway. We aim to provide new ideas and treatment strategies for IL-33/ST2-related drugs to treat different diseases. |
| format | Article |
| id | doaj-art-a7f1e903e8c841d7ab5d590059ba2a17 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a7f1e903e8c841d7ab5d590059ba2a172025-01-24T07:13:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15333351533335IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potentialFeiya Sheng0Mi Li1Jia-Mei Yu2Si-Yu Yang3Liang Zou4Guan-Jun Yang5Le-Le Zhang6Le-Le Zhang7School of Basic Medical Sciences, Chengdu University, Chengdu, ChinaCollege of Pharmacy, Chengdu University, Chengdu, ChinaCollege of Pharmacy, Chengdu University, Chengdu, ChinaCollege of Pharmacy, Chengdu University, Chengdu, ChinaKey Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu, ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro−Products, Ningbo University, Ningbo, ChinaSchool of Basic Medical Sciences, Chengdu University, Chengdu, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, Macao SAR, ChinaInterleukin-33 (IL-33) is a nuclear factor and member of the IL-1 cytokine family. IL-33 is mainly expressed by epithelial and endothelial cells and exerts its function through interaction with various immune cells, and binding to its receptor can form the IL-33/Suppression of tumorigenicity 2 (ST2) signaling pathway. While most cytokines are actively synthesized within cells, IL-33 is produced passively in response to tissue damage or cell necrosis, indicating its role as a signaling molecule following cellular infection, stress, or trauma. IL-33/ST2 signaling pathway has been proved to play diverse role in the pathological process of central nervous system disorders, cancer, fibrosis, autoimmune diseases, etc. Although research on the IL-33/ST2 signaling pathway has deepened recently, relevant treatment strategies have been proposed, and even targeted drugs are in the preclinical stage; further research on the effect of the IL-33/ST2 signaling pathway in different diseases is still necessary, to provide a clearer understanding of the different roles of IL-33/ST2 in disease progression and to develop new drugs and treatment strategies. Because IL-33/ST2 plays an important role in the occurrence and progression of diseases, the study of therapeutic drugs targeting this pathway is also necessary. This review focused on recent studies on the positive or negative role of IL-33/ST2 in different diseases, as well as the current related drugs targeting IL-33/ST2 in the preclinical and clinical stage. The mechanism of IL-33/ST2 in different diseases and its mediating effect on different immune cells have been summarized, as well as the antibody drugs targeting IL-33 or ST2, natural compounds with a mediating effect, and small molecule substances targeting relative pathway. We aim to provide new ideas and treatment strategies for IL-33/ST2-related drugs to treat different diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1533335/fullinterleukin-33suppression of tumorigenicity 2central nervous systemcancerfibrosisautoimmune diseases |
| spellingShingle | Feiya Sheng Mi Li Jia-Mei Yu Si-Yu Yang Liang Zou Guan-Jun Yang Le-Le Zhang Le-Le Zhang IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential Frontiers in Immunology interleukin-33 suppression of tumorigenicity 2 central nervous system cancer fibrosis autoimmune diseases |
| title | IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential |
| title_full | IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential |
| title_fullStr | IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential |
| title_full_unstemmed | IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential |
| title_short | IL-33/ST2 axis in diverse diseases: regulatory mechanisms and therapeutic potential |
| title_sort | il 33 st2 axis in diverse diseases regulatory mechanisms and therapeutic potential |
| topic | interleukin-33 suppression of tumorigenicity 2 central nervous system cancer fibrosis autoimmune diseases |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1533335/full |
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