AccScience Publishing / MI / Online First / DOI: 10.36922/mi.5741
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PERSPECTIVE ARTICLE

SRCR proteins uncovered: Their crucial role in inflammation

Maria Carolina Silva1† ,  Rita P. Pinto1,2† ,  Liliana Oliveira1,3 ,  Alexandre M. Carmo1,3*
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1 i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
2 Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
3 Institute of Molecular and Cell Biology, University of Porto, Porto, Portugal
MI, 5741 https://doi.org/10.36922/mi.5741
Submitted: 1 November 2024 | Revised: 20 December 2024 | Accepted: 6 January 2025 | Published: 17 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The scavenger receptor cysteine-rich (SRCR) superfamily comprises a highly conserved group of extracellular soluble and membrane-attached glycoproteins that function as pattern recognition receptors against a diverse range of pathogenic determinants. While considerable attention has been devoted to their roles in microbial recognition, this perspective aims to emphasize the significant, yet previously overlooked, anti-inflammatory properties of circulating SRCR proteins, which may be even more crucial for immune regulation. In addition, we examine SRCR cell surface proteins that, despite exhibiting limited microbial recognition, have demonstrated potential in mitigating inflammation through their soluble forms released during infectious and inflammatory conditions. Collectively, the paper emphasizes the dual roles of these proteins in infection control and the regulation of inflammatory responses, spotlighting their therapeutic potential in managing inflammatory diseases and enhancing host defense mechanisms.

Keywords
Scavenger receptors
Pattern recognition receptors
Inflammation
Microbial recognition
Immune homeostasis
Funding
This work was supported by National Funds through Fundação para a Ciência e a Tecnologia (FCT), I.P., under the projects 2022.04792.PTDC and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Individual Research Grant to L.O.
Conflict of interest
The authors declare they have no conflict of interest.
References
  1. Martínez VG, Moestrup SK, Holmskov U, Mollenhauer J, Lozano F. The conserved scavenger receptor cysteine-rich superfamily in therapy and diagnosis. Pharmacol Rev. 2011;63(4):967-1000. doi: 10.1124/pr.111.004523

 

  1. Martínez VG, Escoda-Ferran C, Tadeu Simões I, et al. The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression. Cell Mol Immunol. 2014;11(4):343-354. doi: 10.1038/cmi.2014.12

 

  1. Miró-Julià C, Roselló S, Martínez VG, et al. Molecular and functional characterization of mouse S5D-SRCRB: A new group B member of the scavenger receptor cysteine-rich superfamily. J Immunol. 2011;186(4):2344-2354. doi: 10.4049/jimmunol.1000840

 

  1. Bessa Pereira C, Bockova M, Santos RF, et al. The scavenger receptor SSc5D physically interacts with bacteria through the SRCR-containing N-terminal domain. article. Front Immunol. 2016;7:416. doi: 10.3389/fimmu.2016.00416

 

  1. Cardoso MS, Santos RF, Almeida S, et al. Physical interactions with bacteria and protozoan parasites establish the scavenger receptor SSC4D as a broad-spectrum pattern recognition receptor. Front Immunol. 2021;12:760770. doi: 10.3389/fimmu.2021.760770

 

  1. Alharbi AF, Sheng N, Nicol K, Stromberg N, Hollox EJ. Balancing selection at the human salivary agglutinin gene (DMBT1) driven by host-microbe interactions. iScience. 2022;25(5):104189. doi: 10.1016/j.isci.2022.104189

 

  1. Reichhardt MP, Meri S. SALSA: A regulator of the early steps of complement activation on mucosal surfaces. Front Immunol. 2016;7:85. doi: 10.3389/fimmu.2016.00085

 

  1. Muller H, Nagel C, Weiss C, Mollenhauer J, Poeschl J. Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells. BMC Pulm Med. 2015;15:32. doi: 10.1186/s12890-015-0027-x

 

  1. Renner M, Bergmann G, Krebs I, et al. DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn’s disease. Gastroenterology. 2007;133(5):1499-1509. doi: 10.1053/j.gastro.2007.08.007

 

  1. Rosenstiel P, Sina C, End C, et al. Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates bacterial recognition and invasion. J Immunol. 2007;178(12):8203-8211. doi: 10.4049/jimmunol.178.12.8203

 

  1. Sanchez-Moral L, Rafols N, Martori C, Paul T, Tellez E, Sarrias MR. Multifaceted roles of CD5L in infectious and sterile inflammation. Int J Mol Sci. 2021;22(8):4076. doi: 10.3390/ijms22084076

 

  1. Arai S, Miyazaki T. A scavenging system against internal pathogens promoted by the circulating protein apoptosis inhibitor of macrophage (AIM). Semin Immunopathol. 2018;40(6):567-575. doi: 10.1007/s00281-018-0717-6

 

  1. Di Flora DC, Dionizio A, Pereira H, et al. Analysis of plasma proteins involved in inflammation, immune response/ complement system, and blood coagulation upon admission of COVID-19 Patients to hospital may help to predict the prognosis of the disease. Cells. 2023;12(12):1601. doi: 10.3390/cells12121601

 

  1. Yasuda K, Shimodan S, Maehara N, et al. AIM/CD5L ameliorates autoimmune arthritis by promoting removal of inflammatory DAMPs at the lesions. J Autoimmun. 2024;142:103149. doi: 10.1016/j.jaut.2023.103149

 

  1. Fujii T, Yamawaki-Ogata A, Terazawa S, Narita Y, Mutsuga M. Administration of an antibody against apoptosis inhibitor of macrophage prevents aortic aneurysm progression in mice. Sci Rep. 2024;14(1):15878. doi: 10.1038/s41598-024-66791-7

 

  1. Sanjurjo L, Amezaga N, Aran G, et al. The human CD5L/ AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses. Autophagy. 2015;11(3):487-502. doi: 10.1080/15548627.2015.1017183

 

  1. Wang C, Yosef N, Gaublomme J, et al. CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity. Cell. 2015;163(6):1413-1427. doi: 10.1016/j.cell.2015.10.068

 

  1. Weng D, Gao S, Shen H, et al. CD5L attenuates allergic airway inflammation by expanding CD11chigh alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2. Immunology. 2022;167:384-397. doi: 10.1111/imm.13543

 

  1. Gao X, Yan X, Yin Y, et al. Therapeutic targeting of apoptosis inhibitor of macrophage/CD5L in sepsis. Am J Respir Cell Mol Biol. 2019;60(3):323-334. doi: 10.1165/rcmb.2018-0272OC

 

  1. Oliveira L, Silva MC, Gomes AP, et al. CD5L as a promising biological therapeutic for treating sepsis. Nat Commun. 2024;15(1):4119. doi: 10.1038/s41467-024-48360-8

 

  1. Oliveira L, Carmo AM. Response: Commentary: The scavenger receptor SSc5d physically interacts with bacteria through the SRCR-containing N-terminal domain. Front Immunol. 2017;8:1004. doi: 10.3389/fimmu.2017.01004

 

  1. Tarakhovsky A, Kanner SB, Hombach J, et al. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science. 1995;269(5223):535-537. doi: 10.1126/science.7542801

 

  1. Vera J, Fenutría R, Cañadas O, et al. The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome. Proc Natl Acad Sci U S A. 2009;106(5):1506-1511. doi: 10.1073/pnas.0805846106

 

  1. Oliveira MI, Goncalves CM, Pinto M, et al. CD6 attenuates early and late signaling events, setting thresholds for T-cell activation. Eur J Immunol. 2012;42(1):195-205. doi: 10.1002/eji.201040528

 

  1. Sarrias MR, Farnos M, Mota R, et al. CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock. Proc Natl Acad Sci U S A. 2007;104(28):11724-11729. doi: 10.1073/pnas.0702815104

 

  1. Carrasco E, Escoda-Ferran C, Climent N, et al. Human CD6 down-modulation following T-cell activation compromises lymphocyte survival and proliferative responses. Front Immunol. 2017;8:769. doi: 10.3389/fimmu.2017.00769

 

  1. Ramos-Casals M, Font J, García-Carrasco M, et al. High circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren’s syndrome. Rheumatology (Oxford). 2001;40(9):1056-1059. doi: 10.1093/rheumatology/40.9.1056

 

  1. Kragsnaes MS, Jensen JRB, Nilsson AC, et al. Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: Exploratory findings from the FLORA trial. RMD Open. 2024;10(1):e003750. doi: 10.1136/rmdopen-2023-003750

 

  1. Falcon Lincheta L, Saumell Napoles Y, Gray Lovio OR, et al. Long-term therapy with itolizumab is safe and effective for patients with moderate to severe psoriasis: Results from an expanded-access program. Int Immunopharmacol. 2024;134:112225. doi: 10.1016/j.intimp.2024.112225

 

  1. Rodriguez PC, Prada DM, Moreno E, et al. The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: Results from a 6-month, open-label Phase I clinical trial. Clin Exp Immunol. 2018;191(2):229-239. doi: 10.1111/cei.13061

 

  1. Loganathan S, Athalye SN, Joshi SR. Itolizumab, an anti-CD6 monoclonal antibody, as a potential treatment for COVID-19 complications. Expert Opin Biol Ther. 2020;20(9):1025-1031. doi: 10.1080/14712598.2020.1798399

 

  1. Martinez-Florensa M, Consuegra-Fernandez M, Aranda F, et al. Protective effects of human and mouse soluble scavenger-like CD6 lymphocyte receptor in a lethal model of polymicrobial sepsis. Antimicrob Agents Chemother. 2017;61(1):e01391-16. doi: 10.1128/AAC.01391-16

 

  1. Etzerodt A, Moestrup SK. CD163 and inflammation: Biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal. 2013;18(17):2352-2363. doi: 10.1089/ars.2012.4834

 

  1. Mierzchala-Pasierb M, Lipinska-Gediga M, Lewandowski L, Krzystek-Korpacka M. Alterations in serum concentration of soluble CD163 within five study days from ICU admission are associated with in-hospital mortality of septic patients-A preliminary study. Int J Environ Res Public Health. 2023;20(3):2263. doi: 10.3390/ijerph20032263

 

  1. Volfovitch Y, Tsur AM, Gurevitch M, et al. The intercorrelations between blood levels of ferritin, sCD163, and IL-18 in COVID-19 patients and their association to prognosis. Immunol Res. 2022;70(6):817-828. doi: 10.1007/s12026-022-09312-w

 

  1. Thomsen KL, Moller HJ, Graversen JH, et al. Anti- CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats. World J Hepatol. 2016;8(17):726-730. doi: 10.4254/wjh.v8.i17.726

 

  1. Etzerodt A, Moulin M, Doktor TK, et al. Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer. J Exp Med. 2020;217(4):e20191869. doi: 10.1084/jem.20191869

 

  1. Moeller JB, Nielsen MJ, Reichhardt MP, et al. CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response. J Immunol. 2012;188(5):2399-2409. doi: 10.4049/jimmunol.1103150

 

  1. Gonzalez-Dominguez E, Samaniego R, Flores-Sevilla JL, et al. CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo. J Leukoc Biol. 2015;98(4):453-466. doi: 10.1189/jlb.3HI1114-531R
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Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
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