Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications
ABSTRACT Macrophages exhibit remarkable functional plasticity by dynamically polarizing into proinflammatory or antiinflammatory subsets in response to microenvironmental cues. This duality underpins their pivotal roles in immune defense, tissue homeostasis, and disease progression; however, the mol...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
|
| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.70256 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849318399516082176 |
|---|---|
| author | Yongquan Chi Haipeng Jiang Yiyuan Yin Xinyu Zhou Yiyouyou Shao Yongsheng Li Jianhua Rao |
| author_facet | Yongquan Chi Haipeng Jiang Yiyuan Yin Xinyu Zhou Yiyouyou Shao Yongsheng Li Jianhua Rao |
| author_sort | Yongquan Chi |
| collection | DOAJ |
| description | ABSTRACT Macrophages exhibit remarkable functional plasticity by dynamically polarizing into proinflammatory or antiinflammatory subsets in response to microenvironmental cues. This duality underpins their pivotal roles in immune defense, tissue homeostasis, and disease progression; however, the molecular mechanisms governing their polarization and crosstalk across various pathologies remain incompletely defined. This review systematically delineates macrophage biology, emphasizing the interplay between subset‐specific signaling networks and their context‐dependent activation in both health and disease. The heterogeneity of macrophages is characterized by detailing the distinctions between tissue‐resident and monocyte‐derived origins, as well as their polarization states. Core pathways regulating phagocytosis, tissue repair, immune modulation, and neuroprotection are dissected, along with their dysregulation in autoimmune disorders, neurodegeneration, cancers, and cardiovascular diseases. Notably, microenvironmental factors such as damage‐associated molecular patterns, pathogen‐associated molecular patterns, and metabolic intermediates dynamically reshape macrophage phenotypes through NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation or signal transducer and activator of transcription (STAT)‐mediated transcriptional control. Preclinical and clinical evidence underscores potential therapeutic targets and emerging strategies. The significance of this review lies in its integrative analysis of signaling crosstalk, paradoxical pathway roles, and translational implications for precision therapies. These insights into macrophage functions and signaling pathways provide a robust foundation for future disease intervention and personalized medicine. |
| format | Article |
| id | doaj-art-95f7d4ef29164bb4892fff8bc6daf9bf |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-95f7d4ef29164bb4892fff8bc6daf9bf2025-08-20T03:50:49ZengWileyMedComm2688-26632025-07-0167n/an/a10.1002/mco2.70256Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside ApplicationsYongquan Chi0Haipeng Jiang1Yiyuan Yin2Xinyu Zhou3Yiyouyou Shao4Yongsheng Li5Jianhua Rao6Hepatobiliary CenterKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Hepatobiliary CancersThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChinaHepatobiliary CenterKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Hepatobiliary CancersThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChinaNanjing Medical UniversityNanjing Jiangsu ChinaNanjing Medical UniversityNanjing Jiangsu ChinaNanjing Medical UniversityNanjing Jiangsu ChinaDepartment of Medical OncologyChongqing University Cancer HospitalChongqingChinaHepatobiliary CenterKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Hepatobiliary CancersThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChinaABSTRACT Macrophages exhibit remarkable functional plasticity by dynamically polarizing into proinflammatory or antiinflammatory subsets in response to microenvironmental cues. This duality underpins their pivotal roles in immune defense, tissue homeostasis, and disease progression; however, the molecular mechanisms governing their polarization and crosstalk across various pathologies remain incompletely defined. This review systematically delineates macrophage biology, emphasizing the interplay between subset‐specific signaling networks and their context‐dependent activation in both health and disease. The heterogeneity of macrophages is characterized by detailing the distinctions between tissue‐resident and monocyte‐derived origins, as well as their polarization states. Core pathways regulating phagocytosis, tissue repair, immune modulation, and neuroprotection are dissected, along with their dysregulation in autoimmune disorders, neurodegeneration, cancers, and cardiovascular diseases. Notably, microenvironmental factors such as damage‐associated molecular patterns, pathogen‐associated molecular patterns, and metabolic intermediates dynamically reshape macrophage phenotypes through NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation or signal transducer and activator of transcription (STAT)‐mediated transcriptional control. Preclinical and clinical evidence underscores potential therapeutic targets and emerging strategies. The significance of this review lies in its integrative analysis of signaling crosstalk, paradoxical pathway roles, and translational implications for precision therapies. These insights into macrophage functions and signaling pathways provide a robust foundation for future disease intervention and personalized medicine.https://doi.org/10.1002/mco2.70256injury and repairmacrophagemicro‐environmentpolarizationsignaling pathways |
| spellingShingle | Yongquan Chi Haipeng Jiang Yiyuan Yin Xinyu Zhou Yiyouyou Shao Yongsheng Li Jianhua Rao Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications MedComm injury and repair macrophage micro‐environment polarization signaling pathways |
| title | Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications |
| title_full | Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications |
| title_fullStr | Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications |
| title_full_unstemmed | Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications |
| title_short | Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications |
| title_sort | macrophage signaling pathways in health and disease from bench to bedside applications |
| topic | injury and repair macrophage micro‐environment polarization signaling pathways |
| url | https://doi.org/10.1002/mco2.70256 |
| work_keys_str_mv | AT yongquanchi macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications AT haipengjiang macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications AT yiyuanyin macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications AT xinyuzhou macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications AT yiyouyoushao macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications AT yongshengli macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications AT jianhuarao macrophagesignalingpathwaysinhealthanddiseasefrombenchtobedsideapplications |