Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies
Abstract
:1. Introduction
2. Macrophage Infiltration Pattern in OA
3. Functional Diversity of Synovial Macrophages in OA
4. Macrophage Polarization Signals and Modulation of Functional Phenotypes in OA
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Macrophage Subpopulation | Surface Markers/Gene Expression | Clinical Correlates, Proposed Function | Reference |
---|---|---|---|
Synovial macrophages | HLA-DR+, CD14+, CD64+, CD11c+, CD86+, FOLR2+ | iOA and cOA subgroups did not correlate with radiographic measures of disease severity (Kellgren–Lawrence X-ray score), indicators of systemic inflammation, medication | [48] |
Synovial macrophages with pro-inflammatory phenotype (iOA) | Ki67high, E2F8high, CDT1LK1high, CTRLhigh | ||
Synovial macrophages with classical phenotype (cOA) | Ki67low, IGFBP5high, HTRA1high, EFEMP1high, SMAD3high, RUNX2low | ||
Resident macrophages from meniscal tissue | SIGLEC1low, CSF2low, TNFlow | ND | [50] |
Synovial macrophages specific cluster | CD14+ ITGB5+, ADORA3+, MERTK+ | Functional polarization distinct from both M1/M2 | [51] |
M1 | CD11c+ C86+ | Increase in M1/M2 ratio in human knee OA was shown to positively correlate with Kellgren–Lawrence grade | [39] |
M2 | CD206+ CD163+ | ||
Synovial macrophages with inflammatory phenotype (I-MΦ) | HLA-DRAhigh, CD14high, CD16high, IL1Ahigh, IL1Bhigh, IL6high, TNFhigh, CCL2high CCL3high | Proposed to be the main source of inflammatory cytokines | [29] |
Synovial macrophages with immunoregulatory phenotype (IR-MΦ) | HLA-DRAhigh, CD14high, CD163high, STAB1high, TNXIPhigh, CD169high | Proposed immunosuppressive function | [29] |
Resident synovial macrophages | MHCII−, TREM2+, tight junctional proteins | Proposed barrier function | [52] |
Synovial macrophages SC-M1 | CD11c+ CD38+ IL1B+, NR4A2+, HBEGF+, PLAUR+ IFITM3+ | Expression profile matches mouse monocyte-derived synovial macrophages, proposed pro-inflammatory activity | [53] |
Synovial macro-phages SC-M2 | CD14+ CD11c+/−CD38− VSIG4+, GPNMB+, MERTK+, NUPR1+, CTSK+, HTRA1+ | Expression profile matches resident synovial macrophages identified in mice | [52,53] |
Synovial macrophages SC-M3 | CD11c+ CD38+ C1QA+, MARCO+ | Expression profile matches resident synovial macrophages identified in mice | [52,53] |
Synovial macrophages SC-M4 | CD11c+ CD38+ SPP1+, type I and II IFN induced genes, including IFITM3 and IFI6 | Expression profile matches mouse monocyte-derived synovial macrophages | [52,53] |
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Mushenkova, N.V.; Nikiforov, N.G.; Shakhpazyan, N.K.; Orekhova, V.A.; Sadykhov, N.K.; Orekhov, A.N. Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies. Int. J. Mol. Sci. 2022, 23, 8381. https://doi.org/10.3390/ijms23158381
Mushenkova NV, Nikiforov NG, Shakhpazyan NK, Orekhova VA, Sadykhov NK, Orekhov AN. Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies. International Journal of Molecular Sciences. 2022; 23(15):8381. https://doi.org/10.3390/ijms23158381
Chicago/Turabian StyleMushenkova, Nataliya V., Nikita G. Nikiforov, Nikolay K. Shakhpazyan, Varvara A. Orekhova, Nikolay K. Sadykhov, and Alexander N. Orekhov. 2022. "Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies" International Journal of Molecular Sciences 23, no. 15: 8381. https://doi.org/10.3390/ijms23158381