Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics

ABSTRACT Macrophages are heterogeneous immune cells with diverse subtypes and tissue‐specific distributions, displaying dynamic polarization states that critically govern their immunomodulatory functions and responses to environmental cues. As key regulators of innate and adaptive immunity, they ori...

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Main Authors: Mengyuan Peng, Niannian Li, Hongbo Wang, Yaxu Li, Hui Liu, Yanhua Luo, Bao Lang, Weihang Zhang, Shilong Li, Liujun Tian, Bin Liu
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.70304
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author Mengyuan Peng
Niannian Li
Hongbo Wang
Yaxu Li
Hui Liu
Yanhua Luo
Bao Lang
Weihang Zhang
Shilong Li
Liujun Tian
Bin Liu
author_facet Mengyuan Peng
Niannian Li
Hongbo Wang
Yaxu Li
Hui Liu
Yanhua Luo
Bao Lang
Weihang Zhang
Shilong Li
Liujun Tian
Bin Liu
author_sort Mengyuan Peng
collection DOAJ
description ABSTRACT Macrophages are heterogeneous immune cells with diverse subtypes and tissue‐specific distributions, displaying dynamic polarization states that critically govern their immunomodulatory functions and responses to environmental cues. As key regulators of innate and adaptive immunity, they originate from either embryonic progenitors or bone marrow‐derived monocytes and exhibit remarkable plasticity in response to microenvironmental cues. Tissue‐resident macrophages (e.g., Langerhans cells, Kupffer cells, microglia) display unique organ‐specific functions, while inflammatory stimuli drive their polarization into proinflammatory (M1) or anti‐inflammatory (M2) phenotypes along a functional continuum. This review systematically examines macrophage subtypes, their anatomical distribution, and the signaling pathways (e.g., NF‐κB, STATs, PPARγ) underlying polarization shifts in acute and chronic inflammation. We highlight how polarization imbalances contribute to pathologies including neuroinflammation, liver fibrosis, and impaired tissue repair, particularly in aging contexts. Furthermore, we discuss emerging therapeutic strategies targeting macrophage plasticity, such as cytokine modulation, metabolic reprogramming, and subtype‐specific interventions. By integrating recent advances in macrophage biology, this work provides a comprehensive framework for understanding their dual roles in immune regulation and tissue homeostasis, offering insights for treating inflammatory and age‐related diseases through macrophage‐centered immunomodulation.
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spelling doaj-art-a68b04a76b554d74ae340a8e22ac80772025-08-20T03:43:34ZengWileyMedComm2688-26632025-08-0168n/an/a10.1002/mco2.70304Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and TherapeuticsMengyuan Peng0Niannian Li1Hongbo Wang2Yaxu Li3Hui Liu4Yanhua Luo5Bao Lang6Weihang Zhang7Shilong Li8Liujun Tian9Bin Liu10School of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaThe First Affiliated Hospital of Shandong Second Medical University Weifang ChinaThe First Affiliated Hospital of Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaSchool of Anesthesiology Shandong Second Medical University Weifang ChinaABSTRACT Macrophages are heterogeneous immune cells with diverse subtypes and tissue‐specific distributions, displaying dynamic polarization states that critically govern their immunomodulatory functions and responses to environmental cues. As key regulators of innate and adaptive immunity, they originate from either embryonic progenitors or bone marrow‐derived monocytes and exhibit remarkable plasticity in response to microenvironmental cues. Tissue‐resident macrophages (e.g., Langerhans cells, Kupffer cells, microglia) display unique organ‐specific functions, while inflammatory stimuli drive their polarization into proinflammatory (M1) or anti‐inflammatory (M2) phenotypes along a functional continuum. This review systematically examines macrophage subtypes, their anatomical distribution, and the signaling pathways (e.g., NF‐κB, STATs, PPARγ) underlying polarization shifts in acute and chronic inflammation. We highlight how polarization imbalances contribute to pathologies including neuroinflammation, liver fibrosis, and impaired tissue repair, particularly in aging contexts. Furthermore, we discuss emerging therapeutic strategies targeting macrophage plasticity, such as cytokine modulation, metabolic reprogramming, and subtype‐specific interventions. By integrating recent advances in macrophage biology, this work provides a comprehensive framework for understanding their dual roles in immune regulation and tissue homeostasis, offering insights for treating inflammatory and age‐related diseases through macrophage‐centered immunomodulation.https://doi.org/10.1002/mco2.70304inflammationimmunemacrophagespolarizationtherapeuticstissue‐resident macrophages
spellingShingle Mengyuan Peng
Niannian Li
Hongbo Wang
Yaxu Li
Hui Liu
Yanhua Luo
Bao Lang
Weihang Zhang
Shilong Li
Liujun Tian
Bin Liu
Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
MedComm
inflammation
immune
macrophages
polarization
therapeutics
tissue‐resident macrophages
title Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
title_full Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
title_fullStr Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
title_full_unstemmed Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
title_short Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
title_sort macrophages subtypes distribution polarization immunomodulatory functions and therapeutics
topic inflammation
immune
macrophages
polarization
therapeutics
tissue‐resident macrophages
url https://doi.org/10.1002/mco2.70304
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