IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8
Abstract Innate immunity is the first line of host defense and contributes to pain. However, how innate immune system interacts with sensory neurons to govern pain remains poorly understood. Here, we report that interleukin 33(IL-33) initiates pain hypersensitivity that requires chemokine (C-C motif...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08119-3 |
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| author | Linjie Wang Jingyun Zhang Shijuan Qiu Ruizhen Huang Yuge Wang Yuting Wang Mingyu Li Qingqing Ye Sibo Zhang Zhenhua Qi Lan Cao Guohao Li Yajie An Denghui Xie Wenli Mi Huaqiao Wang Tao Luo Jingdun Xie Junting Huang |
| author_facet | Linjie Wang Jingyun Zhang Shijuan Qiu Ruizhen Huang Yuge Wang Yuting Wang Mingyu Li Qingqing Ye Sibo Zhang Zhenhua Qi Lan Cao Guohao Li Yajie An Denghui Xie Wenli Mi Huaqiao Wang Tao Luo Jingdun Xie Junting Huang |
| author_sort | Linjie Wang |
| collection | DOAJ |
| description | Abstract Innate immunity is the first line of host defense and contributes to pain. However, how innate immune system interacts with sensory neurons to govern pain remains poorly understood. Here, we report that interleukin 33(IL-33) initiates pain hypersensitivity that requires chemokine (C-C motif) ligand 2 (CCL2) secretion from infiltrated macrophages and neutrophils and activation of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) channels in sensory neurons. Blocking CCL2 receptor (CCR2) attenuates IL-33- induced and Complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia and blocking TRPV1 and TRPM8 attenuates IL-33-induced mechanical and thermal hypersensitivity and cold allodynia respectively. Furthermore, depletion of macrophages reduces IL-33-induced pain and expression of CCL2 and suppression of tumorigenicity 2 (ST2) in hindpaw skin and inhibition of CCR2 prevents recruitment of macrophages and neutrophils. Our findings reveal an unrecognized neuroimmune crosstalk of IL-33-CCL2 signaling from infiltrated immune cells with TRPV1/TRPM8 in sensory neurons to facilitate pain states. |
| format | Article |
| id | doaj-art-2cec9e3daa1b4fbbb703d6d6b6387dcf |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-2cec9e3daa1b4fbbb703d6d6b6387dcf2025-08-20T03:43:26ZengNature PortfolioCommunications Biology2399-36422025-05-018111510.1038/s42003-025-08119-3IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8Linjie Wang0Jingyun Zhang1Shijuan Qiu2Ruizhen Huang3Yuge Wang4Yuting Wang5Mingyu Li6Qingqing Ye7Sibo Zhang8Zhenhua Qi9Lan Cao10Guohao Li11Yajie An12Denghui Xie13Wenli Mi14Huaqiao Wang15Tao Luo16Jingdun Xie17Junting Huang18Department of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterFoshan Clinical Medical School, Guangzhou University of Chinese MedicineDepartment of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Fudan UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterDepartment of Human Anatomy and Physiology, Zhongshan School of Medicine, Sun Yat-Sen UniversityAbstract Innate immunity is the first line of host defense and contributes to pain. However, how innate immune system interacts with sensory neurons to govern pain remains poorly understood. Here, we report that interleukin 33(IL-33) initiates pain hypersensitivity that requires chemokine (C-C motif) ligand 2 (CCL2) secretion from infiltrated macrophages and neutrophils and activation of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential melastatin 8 (TRPM8) channels in sensory neurons. Blocking CCL2 receptor (CCR2) attenuates IL-33- induced and Complete Freund’s adjuvant (CFA)-induced thermal hyperalgesia and blocking TRPV1 and TRPM8 attenuates IL-33-induced mechanical and thermal hypersensitivity and cold allodynia respectively. Furthermore, depletion of macrophages reduces IL-33-induced pain and expression of CCL2 and suppression of tumorigenicity 2 (ST2) in hindpaw skin and inhibition of CCR2 prevents recruitment of macrophages and neutrophils. Our findings reveal an unrecognized neuroimmune crosstalk of IL-33-CCL2 signaling from infiltrated immune cells with TRPV1/TRPM8 in sensory neurons to facilitate pain states.https://doi.org/10.1038/s42003-025-08119-3 |
| spellingShingle | Linjie Wang Jingyun Zhang Shijuan Qiu Ruizhen Huang Yuge Wang Yuting Wang Mingyu Li Qingqing Ye Sibo Zhang Zhenhua Qi Lan Cao Guohao Li Yajie An Denghui Xie Wenli Mi Huaqiao Wang Tao Luo Jingdun Xie Junting Huang IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8 Communications Biology |
| title | IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8 |
| title_full | IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8 |
| title_fullStr | IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8 |
| title_full_unstemmed | IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8 |
| title_short | IL-33/ST2 drives inflammatory pain via CCL2 signaling and activation of TRPV1 and TRPM8 |
| title_sort | il 33 st2 drives inflammatory pain via ccl2 signaling and activation of trpv1 and trpm8 |
| url | https://doi.org/10.1038/s42003-025-08119-3 |
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