Advances in the Study of Macrophage Polarization in Inflammatory Immune Skin Diseases

Overview

Journal J Inflamm (Lond)

Publisher Biomed Central

Date 2023 Oct 12

PMID 37828492

Authors

Tingting Xia

Shengping Fu

Ruilin Yang

Kang Yang

Wei Lei

Ying Yang

Qian Zhang

Yujie Zhao

Jiang Yu

Limei Yu

Tao Zhang

Affiliations

Soon will be listed here.

Abstract

When exposed to various microenvironmental stimuli, macrophages are highly plastic and primarily polarized into the pro-inflammatory M1-type and the anti-inflammatory M2-type, both of which perform almost entirely opposing functions. Due to this characteristic, macrophages perform different functions at different stages of immunity and inflammation. Inflammatory immune skin diseases usually show an imbalance in the M1/M2 macrophage ratio, and altering the macrophage polarization phenotype can either make the symptoms worse or better. Therefore, this review presents the mechanisms of macrophage polarization, inflammation-related signaling pathways (JAK/STAT, NF-κB, and PI3K/Akt), and the role of both in inflammatory immune skin diseases (psoriasis, AD, SLE, BD, etc.) to provide new directions for basic and clinical research of related diseases.

Citing Articles

Bacterial-Mediated In Situ Engineering of Tumour-Associated Macrophages for Cancer Immunotherapy.

Kuhl G, Tangney M Cancers (Basel). 2025; 17(5).

PMID: 40075571 PMC: 11899205. DOI: 10.3390/cancers17050723.

Molecular Mechanisms Underlying Heart Failure and Their Therapeutic Potential.

Fonseka O, Gare S, Chen X, Zhang J, Alatawi N, Ross C Cells. 2025; 14(5).

PMID: 40072053 PMC: 11899429. DOI: 10.3390/cells14050324.

Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.

Guan F, Wang R, Yi Z, Luo P, Liu W, Xie Y Signal Transduct Target Ther. 2025; 10(1):93.

PMID: 40055311 PMC: 11889221. DOI: 10.1038/s41392-025-02124-y.

Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets.

Raoufi A, Soleimani Samarkhazan H, Nouri S, Khaksari M, Abbasi Sourki P, Sargazi Aval O Clin Exp Med. 2025; 25(1):73.

PMID: 40048037 PMC: 11885342. DOI: 10.1007/s10238-025-01588-0.

Dual-Action flavonol carbonized polymer dots spray: Accelerating burn wound recovery through immune responses modulation and EMT induction.

Du L, Zhang X, Huang L, Yang M, Zhang W, Xu J Mater Today Bio. 2025; 31:101572.

PMID: 40034983 PMC: 11872610. DOI: 10.1016/j.mtbio.2025.101572.

References

van der Zande H, Nitsche D, Schlautmann L, Guigas B, Burgdorf S . The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation. Front Immunol. 2021; 12:765034. PMC: 8551360. DOI: 10.3389/fimmu.2021.765034. View

He Y, Gao Y, Zhang Q, Zhou G, Cao F, Yao S . IL-4 Switches Microglia/macrophage M1/M2 Polarization and Alleviates Neurological Damage by Modulating the JAK1/STAT6 Pathway Following ICH. Neuroscience. 2020; 437:161-171. DOI: 10.1016/j.neuroscience.2020.03.008. View

Liu T, Deng Z, Xie H, Chen M, Xu S, Peng Q . ADAMDEC1 promotes skin inflammation in rosacea via modulating the polarization of M1 macrophages. Biochem Biophys Res Commun. 2019; 521(1):64-71. DOI: 10.1016/j.bbrc.2019.10.073. View

Lapi I, Daskalaki M, Axarlis K, Paflioti E, Tsichlis P, Vergadi E . AKT Isoforms in Macrophage Activation, Polarization, and Survival. Curr Top Microbiol Immunol. 2022; 436:165-196. DOI: 10.1007/978-3-031-06566-8_7. View

van Zuuren E, Arents B, van der Linden M, Vermeulen S, Fedorowicz Z, Tan J . Rosacea: New Concepts in Classification and Treatment. Am J Clin Dermatol. 2021; 22(4):457-465. PMC: 8200341. DOI: 10.1007/s40257-021-00595-7. View

Ma C, Xia Y, Yang Q, Zhao Y . The contribution of macrophages to systemic lupus erythematosus. Clin Immunol. 2019; 207:1-9. DOI: 10.1016/j.clim.2019.06.009. View

Arango Duque G, Descoteaux A . Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol. 2014; 5:491. PMC: 4188125. DOI: 10.3389/fimmu.2014.00491. View

Jeon H, Oh S, Kum E, Seo S, Park Y, Kim G . Immunomodulatory Effects of an Aqueous Extract of Black Radish on Mouse Macrophages via the TLR2/4-Mediated Signaling Pathway. Pharmaceuticals (Basel). 2022; 15(11). PMC: 9697478. DOI: 10.3390/ph15111376. View

Sun W, Yan S, Yang C, Yang J, Wang H, Li C . Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice. Immunol Invest. 2022; 51(6):1785-1803. DOI: 10.1080/08820139.2022.2055478. View

10.

Linton M, Moslehi J, Babaev V . Akt Signaling in Macrophage Polarization, Survival, and Atherosclerosis. Int J Mol Sci. 2019; 20(11). PMC: 6600269. DOI: 10.3390/ijms20112703. View

11.

Arranz A, Doxaki C, Vergadi E, Martinez De La Torre Y, Vaporidi K, Lagoudaki E . Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci U S A. 2012; 109(24):9517-22. PMC: 3386059. DOI: 10.1073/pnas.1119038109. View

12.

Chen D, Li H, Li W, Feng S, Deng D . and Its Methoxyflavones: Chemistry and Biological Activities. Evid Based Complement Alternat Med. 2019; 2018:4057456. PMC: 6311295. DOI: 10.1155/2018/4057456. View

13.

Boutilier A, Elsawa S . Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci. 2021; 22(13). PMC: 8268869. DOI: 10.3390/ijms22136995. View

14.

Drozina G, Kohoutek J, Jabrane-Ferrat N, Peterlin B . Expression of MHC II genes. Curr Top Microbiol Immunol. 2006; 290:147-70. DOI: 10.1007/3-540-26363-2_7. View

15.

Chen X, Tang L, Fu Y, Wang Y, Han Z, Meng J . Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages. Int J Mol Med. 2017; 40(6):1921-1931. DOI: 10.3892/ijmm.2017.3161. View

16.

Acosta-Martinez M, Cabail M . The PI3K/Akt Pathway in Meta-Inflammation. Int J Mol Sci. 2022; 23(23). PMC: 9740745. DOI: 10.3390/ijms232315330. View

17.

Cutolo M, Campitiello R, Gotelli E, Soldano S . The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis. Front Immunol. 2022; 13:867260. PMC: 9161083. DOI: 10.3389/fimmu.2022.867260. View

18.

Gu S, Dai H, Zhao X, Gui C, Gui J . AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling. Aging (Albany NY). 2020; 12(8):6928-6946. PMC: 7202485. DOI: 10.18632/aging.103051. View

19.

Parra Sanchez A, Voskuyl A, van Vollenhoven R . Treat-to-target in systemic lupus erythematosus: advancing towards its implementation. Nat Rev Rheumatol. 2022; 18(3):146-157. DOI: 10.1038/s41584-021-00739-3. View

20.

Gao S, Mao F, Zhang B, Zhang L, Zhang X, Wang M . Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-κB and signal transducer and activator of transcription 3 pathways. Exp Biol Med (Maywood). 2014; 239(3):366-75. DOI: 10.1177/1535370213518169. View