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Review
. 2022 Oct 17:13:1012002.
doi: 10.3389/fimmu.2022.1012002. eCollection 2022.

The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer

Jack Gudgeon  1 , José Luis Marín-Rubio  1 , Matthias Trost  1
Affiliations
Review

The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer

Jack Gudgeon et al. Front Immunol. .

Abstract

Macrophage scavenger receptor 1 (MSR1), also named CD204, holds key inflammatory roles in multiple pathophysiologic processes. Present primarily on the surface of various types of macrophage, this receptor variably affects processes such as atherosclerosis, innate and adaptive immunity, lung and liver disease, and more recently, cancer. As highlighted throughout this review, the role of MSR1 is often dichotomous, being either host protective or detrimental to the pathogenesis of disease. We will discuss the role of MSR1 in health and disease with a focus on the molecular mechanisms influencing MSR1 expression, how altered expression affects disease process and macrophage function, the limited cell signalling pathways discovered thus far, the emerging role of MSR1 in tumour associated macrophages as well as the therapeutic potential of targeting MSR1.

Keywords: CD204; MSR1; cancer; immunology; inflammation; macrophages.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Classification of scavenger receptors and MSR1 isoforms. Schematic representation of different classes of scavenger receptors. Individual domains are identified in the key within the figure.
Figure 2
Figure 2
Functional domain organisation of MSR1, including corresponding amino acid (aa) positions and post-translational modification sites relevant to signalling.
Figure 3
Figure 3
MSR1 expression in (A) normal human tissues and (B) human immune cells. Human tissue expression measured by RNA sequencing abundance of MSR1 transcripts, using a normalization method to calculate transcripts per million (TPM), determined by the GTEx Project (49). Human immune cell MSR1 expression measured by RNAseq as part of the human protein (HPA) database (proteinatlas.org) (50).
Figure 4
Figure 4
Genetic alterations of MSR1 in human tumour tissues. Data obtained from TCGA PanCancer Atlas Studies in 10967 tumour samples from various origins.
Figure 5
Figure 5
Transcription factors of MSR1 promoter. Binding sites of transcription factors in the promoter of MSR1 from experimental and theoretical sources from the TF2DNA database (70).
Figure 6
Figure 6
Signalling pathways downstream of MSR1 initiated after specific ligand binding. Question marks within the figure highlight gaps in the knowledge regarding each pathway.
Figure 7
Figure 7
Signalling complex recruitment to MSR1 in M2 macrophages. Triggering of MSR1 by fucoidan, oxidised LDL (ox-LDL) or saturated fatty acids (SFAs) induces MSR1 K63 polyubiquitylation at K27, mediated by an unknown E3 ligase. This polyubiquitin chain acts as a scaffold for recruitment and activation of the TAK1/MKK7/JNK signalling complex. This stimulates a pro-inflammatory phenotypic switch within M2 macrophages.
Figure 8
Figure 8
Overview of the involvement of MSR1 in health and disease states.
Figure 9
Figure 9
Overview of MSR1-positive TAMs signalling. Macrophages become polarised towards the M2-like tumour-associated macrophage (TAM) phenotype by tumour derived factors such as IL-4 and CSF-1. Once polarised they then support tumour expansion and metastasis by secreting factors that influence several of the hallmarks of cancer. They suppress the immune system by regulating the function of Treg (Regulatory T cells) and cytotoxic T cells (CD8+). Metastasis and growth are facilitated through breakdown of the extracellular matrix (ECM), the induction of angiogenesis and lymphangiogenesis, and directly through cytokine mediated influence of tumour cell motility. Adrenomedullin (ADM); colony stimulating factor 1 (CSF-1); epidermal growth factor (EGF); interleukin (IL); matrix metalloproteinases (MMPs); monocyte chemoattractant protein-1 (MCP-1); placental growth factor (PlGF); platelet-derived growth factor (PDGF); programmed death-ligand 1 (PDL1); prostaglandin E1 (PGE-1); transforming growth factor beta (TGFb); urokinase plasminogen activator (uPa); vascular endothelial growth factor A (VEGFA).
Figure 10
Figure 10
Overview of the processes and diseases where MSR1 holds either a protective or damaging function. Arrows indicate whether expression of MSR1 is increased or decreased.
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References

    1. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol (2005) 5:953–64. doi: 10.1038/nri1733 - DOI - PubMed
    1. Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: Different gene signatures in M1(LPS+) vs. classically and M2(LPS–) vs. alternatively activated macrophages. Front Immunol (2019) 10:1084. doi: 10.3389/fimmu.2019.01084 - DOI - PMC - PubMed
    1. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. . Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity (2014) 41:14–20. doi: 10.1016/j.immuni.2014.06.008 - DOI - PMC - PubMed
    1. Labonte AC, Sung S-SJ, Jennelle LT, Dandekar AP, Hahn YS. Expression of scavenger receptor-AI promotes alternative activation of murine macrophages to limit hepatic inflammation and fibrosis. Hepatology (2017) 65:32–43. doi: 10.1002/hep.28873 - DOI - PMC - PubMed
    1. Goldstein JL, Ho YK, Basu SK, Brown MS. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci (1979) 76:333–7. doi: 10.1073/pnas.76.1.333 - DOI - PMC - PubMed

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