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生长分化因子15在心血管疾病中的诊疗作用及其研究进展
The Diagnostic and Therapeutic Roles of Growth Differentiation Factor 15 in Cardiovascular Diseases and Its Research Progress

DOI: 10.12677/acm.2024.14112973, PP. 985-994

Keywords: 生长分化因子15,心血管疾病,诊断,预后,治疗
Growth Differentiation Factor 15
, Cardiovascular Diseases, Diagnosis, Prognosis, Treatment

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Abstract:

目前,心血管疾病如动脉粥样硬化、心肌梗死、心脏肥大和心力衰竭等是全球主要的死亡原因,严重危害人类的生命安全,因此,心血管疾病的早期诊断、预后监测及治疗至关重要。近年来,生物标志物在心血管疾病患者的诊断和预后评估中具有越来越重要的临床价值。其中,生长分化因子15 (growth differentiation factor 15, GDF15)是一种新兴的心血管疾病生物标志物,是死亡率和不良预后的独立预测因子。许多基础研究还表明,GDF15在心血管疾病中发挥保护作用,可能具有潜在的治疗价值。本文就GDF15在心血管疾病中的诊疗作用及相关研究进展做一综述,旨在探索GDF15在心血管疾病诊断、预后监测和治疗中的应用前景。
Currently, cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, cardiac hypertrophy, and heart failure are the leading causes of death globally, posing a serious threat to human life safety. Therefore, early diagnosis, prognosis monitoring, and treatment of CVDs are crucial. In recent years, biomarkers have become increasingly important in the diagnosis and prognosis assessment of patients with CVDs. Among them, growth differentiation factor 15 (GDF15) is an emerging biomarker for CVDs and an independent predictor of mortality and poor prognosis. Many basic research studies have also indicated that GDF15 plays a protective role in CVDs and may have potential therapeutic value. This article reviews the diagnostic and therapeutic roles of GDF15 in CVDs and related research progress, aiming to explore the application prospects of GDF15 in the diagnosis, prognosis monitoring, and treatment of CVDs.

References

[1]  Widmer, R.J., Flammer, A.J., Lerman, L.O. and Lerman, A. (2015) The Mediterranean Diet, Its Components, and Cardiovascular Disease. The American Journal of Medicine, 128, 229-238.
https://doi.org/10.1016/j.amjmed.2014.10.014
[2]  Nyárády, B.B., Kiss, L.Z., Bagyura, Z., Merkely, B., Dósa, E., Láng, O., et al. (2024) Growth and Differentiation Factor-15: A Link between Inflammaging and Cardiovascular Disease. Biomedicine & Pharmacotherapy, 174, Article ID: 116475.
https://doi.org/10.1016/j.biopha.2024.116475
[3]  Eddy, A.C. and Trask, A.J. (2021) Growth Differentiation Factor-15 and Its Role in Diabetes and Cardiovascular Disease. Cytokine & Growth Factor Reviews, 57, 11-18.
https://doi.org/10.1016/j.cytogfr.2020.11.002
[4]  Smith, S.C. (2011) Reducing the Global Burden of Ischemic Heart Disease and Stroke: A Challenge for the Cardiovascular Community and the United Nations. Circulation, 124, 278-279.
https://doi.org/10.1161/circulationaha.111.040170
[5]  Teo, K.K. and Rafiq, T. (2021) Cardiovascular Risk Factors and Prevention: A Perspective from Developing Countries. Canadian Journal of Cardiology, 37, 733-743.
https://doi.org/10.1016/j.cjca.2021.02.009
[6]  Nyárády, B.B., Kiss, L.Z., Bagyura, Z., Merkely, B., Dósa, E., Láng, O., et al. (2024) Growth and Differentiation Factor-15: A Link between Inflammaging and Cardiovascular Disease. Biomedicine & Pharmacotherapy, 174, Article ID: 116475.
https://doi.org/10.1016/j.biopha.2024.116475
[7]  Rohatgi, A., Patel, P., Das, S.R., Ayers, C.R., Khera, A., Martinez-Rumayor, A., et al. (2012) Association of Growth Differentiation Factor-15 with Coronary Atherosclerosis and Mortality in a Young, Multiethnic Population: Observations from the Dallas Heart Study. Clinical Chemistry, 58, 172-182.
https://doi.org/10.1373/clinchem.2011.171926
[8]  May, B.M., Pimentel, M., Zimerman, L.I. and Rohde, L.E. (2021) GDF-15 como Biomarcador em Doenças Cardiovasculares. Arquivos Brasileiros de Cardiologia, 116, 494-500.
https://doi.org/10.36660/abc.20200426
[9]  Corre, J., Hébraud, B. and Bourin, P. (2013) Concise Review: Growth Differentiation Factor 15 in Pathology: A Clinical Role? Stem Cells Translational Medicine, 2, 946-952.
https://doi.org/10.5966/sctm.2013-0055
[10]  Rochette, L., Dogon, G., Zeller, M., Cottin, Y. and Vergely, C. (2021) GDF15 and Cardiac Cells: Current Concepts and New Insights. International Journal of Molecular Sciences, 22, Article 8889.
https://doi.org/10.3390/ijms22168889
[11]  Gerstein, H.C., Pare, G., Hess, S., Ford, R.J., Sjaarda, J., Raman, K., et al. (2016) Growth Differentiation Factor 15 as a Novel Biomarker for Metformin. Diabetes Care, 40, 280-283.
https://doi.org/10.2337/dc16-1682
[12]  Adela, R. and Banerjee, S.K. (2015) GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. Journal of Diabetes Research, 2015, Article ID: 490842.
https://doi.org/10.1155/2015/490842
[13]  Xu, J., Kimball, T.R., Lorenz, J.N., Brown, D.A., Bauskin, A.R., Klevitsky, R., et al. (2006) GDF15/MIC-1 Functions as a Protective and Antihypertrophic Factor Released from the Myocardium in Association with SMAD Protein Activation. Circulation Research, 98, 342-350.
https://doi.org/10.1161/01.res.0000202804.84885.d0
[14]  Jung, S., Choi, M.J., Ryu, D., Yi, H., Lee, S.E., Chang, J.Y., et al. (2018) Reduced Oxidative Capacity in Macrophages Results in Systemic Insulin Resistance. Nature Communications, 9, Article No. 1551.
https://doi.org/10.1038/s41467-018-03998-z
[15]  Artz, A., Butz, S. and Vestweber, D. (2016) GDF-15 Inhibits Integrin Activation and Mouse Neutrophil Recruitment through the Alk-5/TGF-βRII Heterodimer. Blood, 128, 529-541.
https://doi.org/10.1182/blood-2016-01-696617
[16]  Hu, H., Chen, D., Wang, Y., Feng, Y., Cao, G., Vaziri, N.D., et al. (2018) New Insights into TGF-β/Smad Signaling in Tissue Fibrosis. Chemico-Biological Interactions, 292, 76-83.
https://doi.org/10.1016/j.cbi.2018.07.008
[17]  Kim, K.H., Han, J.W., Jung, S., Park, B., Han, C.W. and Joo, M. (2017) Kaurenoic Acid Activates TGF-β Signaling. Phytomedicine, 32, 8-14.
https://doi.org/10.1016/j.phymed.2017.04.008
[18]  Park, S., Cho, H., Jeong, Y., Shin, J., Kang, J., Park, K., et al. (2014) Melittin Inhibits TGF-β-Induced Pro-Fibrotic Gene Expression through the Suppression of the TGFβRII-Smad, ERK1/2 and JNK-Mediated Signaling Pathway. The American Journal of Chinese Medicine, 42, 1139-1152.
https://doi.org/10.1142/s0192415x14500712
[19]  Zhu, X., Lu, J., Rao, J., Ru, D., Gao, M., Shi, D., et al. (2023) Crosstalk between Interleukin-1 Receptor-Like 1 and Transforming Growth Factor-β Receptor Signaling Promotes Renal Fibrosis. The American Journal of Pathology, 193, 1029-1045.
https://doi.org/10.1016/j.ajpath.2023.05.002
[20]  Strowitzki, M.J., Ritter, A.S., Kimmer, G. and Schneider, M. (2019) Hypoxia-Adaptive Pathways: A Pharmacological Target in Fibrotic Disease? Pharmacological Research, 147, Article ID: 104364.
https://doi.org/10.1016/j.phrs.2019.104364
[21]  Watson, W.H., Ritzenthaler, J.D. and Roman, J. (2016) Lung Extracellular Matrix and Redox Regulation. Redox Biology, 8, 305-315.
https://doi.org/10.1016/j.redox.2016.02.005
[22]  Wang, J., Wei, L., Yang, X. and Zhong, J. (2019) Roles of Growth Differentiation Factor 15 in Atherosclerosis and Coronary Artery Disease. Journal of the American Heart Association, 8, e012826.
https://doi.org/10.1161/jaha.119.012826
[23]  Zheng, D., Huo, M., Li, B., Wang, W., Piao, H., Wang, Y., et al. (2021) The Role of Exosomes and Exosomal MicroRNA in Cardiovascular Disease. Frontiers in Cell and Developmental Biology, 8, Article 616161.
https://doi.org/10.3389/fcell.2020.616161
[24]  Pirillo, A., Norata, G.D. and Catapano, A.L. (2013) LOX-1, OxLDL, and Atherosclerosis. Mediators of Inflammation, 2013, Article ID: 152786.
https://doi.org/10.1155/2013/152786
[25]  Liuizė (Abramavičiūtė), A. and Mongirdienė, A. (2024) TGF-β Isoforms and GDF-15 in the Development and Progression of Atherosclerosis. International Journal of Molecular Sciences, 25, Article 2104.
https://doi.org/10.3390/ijms25042104
[26]  Huang, H., Chen, Z., Li, Y., Gong, K., Xiao, L., Fu, H., et al. (2021) GDF-15 Suppresses Atherosclerosis by Inhibiting OxLDL-Induced Lipid Accumulation and Inflammation in Macrophages. Evidence-Based Complementary and Alternative Medicine, 2021, Article ID: 6497568.
https://doi.org/10.1155/2021/6497568
[27]  Aguilar-Recarte, D., Barroso, E., Gumà, A., Pizarro-Delgado, J., Peña, L., Ruart, M., et al. (2021) GDF15 Mediates the Metabolic Effects of PPARβ/δ by activating AMPK. Cell Reports, 36, Article ID: 109501.
https://doi.org/10.1016/j.celrep.2021.109501
[28]  Sawalha, K., Norgard, N.B., Drees, B.M. and López-Candales, A. (2023) Growth Differentiation Factor 15 (GDF-15), a New Biomarker in Heart Failure Management. Current Heart Failure Reports, 20, 287-299.
https://doi.org/10.1007/s11897-023-00610-4
[29]  Echouffo-Tcheugui, J.B., Daya, N., Ndumele, C.E., Matsushita, K., Hoogeveen, R.C., Ballantyne, C.M., et al. (2022) Diabetes, GDF-15 and Incident Heart Failure: The Atherosclerosis Risk in Communities Study. Diabetologia, 65, 955-963.
https://doi.org/10.1007/s00125-022-05678-6
[30]  Rathnayake, N., Buhlin, K., Kjellström, B., Klinge, B., Löwbeer, C., Norhammar, A., et al. (2017) Saliva and Plasma Levels of Cardiac‐Related Biomarkers in Post‐myocardial Infarction Patients. Journal of Clinical Periodontology, 44, 692-699.
https://doi.org/10.1111/jcpe.12740
[31]  Kempf, T., Eden, M., Strelau, J., Naguib, M., Willenbockel, C., Tongers, J., et al. (2006) The Transforming Growth Factor-Β Superfamily Member Growth-Differentiation Factor-15 Protects the Heart from Ischemia/Reperfusion Injury. Circulation Research, 98, 351-360.
https://doi.org/10.1161/01.res.0000202805.73038.48
[32]  Unsicker, K., Spittau, B. and Krieglstein, K. (2013) The Multiple Facets of the TGF-β Family Cytokine Growth/Differentiation Factor-15/Macrophage Inhibitory Cytokine-1. Cytokine & Growth Factor Reviews, 24, 373-384.
https://doi.org/10.1016/j.cytogfr.2013.05.003
[33]  Kempf, T., Zarbock, A., Widera, C., Butz, S., Stadtmann, A., Rossaint, J., et al. (2011) GDF-15 Is an Inhibitor of Leukocyte Integrin Activation Required for Survival after Myocardial Infarction in Mice. Nature Medicine, 17, 581-588.
https://doi.org/10.1038/nm.2354
[34]  Lorell, B.H. and Carabello, B.A. (2000) Left Ventricular Hypertrophy. Circulation, 102, 470-479.
https://doi.org/10.1161/01.cir.102.4.470
[35]  Weintraub, R.G., Semsarian, C. and Macdonald, P. (2017) Dilated Cardiomyopathy. The Lancet, 390, 400-414.
https://doi.org/10.1016/s0140-6736(16)31713-5
[36]  Hauser, J.A., Demyanets, S., Rusai, K., Goritschan, C., Weber, M., Panesar, D., et al. (2016) Diagnostic Performance and Reference Values of Novel Biomarkers of Paediatric Heart Failure. Heart, 102, 1633-1639.
https://doi.org/10.1136/heartjnl-2016-309460
[37]  Kou, H., Jin, X., Gao, D., Ma, R., Dong, X., Wei, J., et al. (2017) Association between Growth Differentiation Factor 15 and Left Ventricular Hypertrophy in Hypertensive Patients and Healthy Adults. Clinical and Experimental Hypertension, 40, 8-15.
https://doi.org/10.1080/10641963.2016.1273948
[38]  Xue, H., Fu, Z., Chen, Y., Xing, Y., Liu, J., Zhu, H., et al. (2012) The Association of Growth Differentiation Factor-15 with Left Ventricular Hypertrophy in Hypertensive Patients. PLOS ONE, 7, e46534.
https://doi.org/10.1371/journal.pone.0046534
[39]  Stahrenberg, R., Edelmann, F., Mende, M., Kockskämper, A., Düngen, H., Lüers, C., et al. (2010) The Novel Biomarker Growth Differentiation Factor 15 in Heart Failure with Normal Ejection Fraction. European Journal of Heart Failure, 12, 1309-1316.
https://doi.org/10.1093/eurjhf/hfq151
[40]  Xu, X., Nie, Y., Wang, F., Bai, Y., Lv, Z., Zhang, Y., et al. (2014) Growth Differentiation Factor (GDF)-15 Blocks Norepinephrine-Induced Myocardial Hypertrophy via a Novel Pathway Involving Inhibition of Epidermal Growth Factor Receptor Transactivation. Journal of Biological Chemistry, 289, 10084-10094.
https://doi.org/10.1074/jbc.m113.516278
[41]  Piek, A., Du, W., de Boer, R.A. and Silljé, H.H.W. (2018) Novel Heart Failure Biomarkers: Why Do We Fail to Exploit Their Potential? Critical Reviews in Clinical Laboratory Sciences, 55, 246-263.
https://doi.org/10.1080/10408363.2018.1460576
[42]  Sharma, A., Stevens, S.R., Lucas, J., Fiuzat, M., Adams, K.F., Whellan, D.J., et al. (2017) Utility of Growth Differentiation Factor-15, a Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure: Insights from the HF-ACTION Study. JACC: Heart Failure, 5, 724-734.
https://doi.org/10.1016/j.jchf.2017.07.013
[43]  Ponikowski, P., Voors, A.A., Anker, S.D., Bueno, H., Cleland, J.G.F., Coats, A.J.S., et al. (2016) 2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. European Heart Journal, 37, 2129-2200.
https://doi.org/10.1093/eurheartj/ehw128
[44]  Meijers, W.C., Bayes‐Genis, A., Mebazaa, A., Bauersachs, J., Cleland, J.G.F., Coats, A.J.S., et al. (2021) Circulating Heart Failure Biomarkers Beyond Natriuretic Peptides: Review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC). European Journal of Heart Failure, 23, 1610-1632.
https://doi.org/10.1002/ejhf.2346
[45]  Santhanakrishnan, R., Chong, J.P.C., Ng, T.P., Ling, L.H., Sim, D., Toh G. Leong, K., et al. (2012) Growth Differentiation Factor 15, ST2, High‐Sensitivity Troponin T, and N‐Terminal Pro Brain Natriuretic Peptide in Heart Failure with Preserved vs. Reduced Ejection Fraction. European Journal of Heart Failure, 14, 1338-1347.
https://doi.org/10.1093/eurjhf/hfs130
[46]  Maisel, A. (2007) Biomarkers in Heart Failure. Does Prognostic Utility Translate to Clinical Futility? Journal of the American College of Cardiology, 50, 1061-1063.
https://doi.org/10.1016/j.jacc.2007.05.032
[47]  Kempf, T., von Haehling, S., Peter, T., Allhoff, T., Cicoira, M., Doehner, W., et al. (2007) Prognostic Utility of Growth Differentiation Factor-15 in Patients with Chronic Heart Failure. Journal of the American College of Cardiology, 50, 1054-1060.
https://doi.org/10.1016/j.jacc.2007.04.091
[48]  Ye, B., Fan, X., Fang, Z., Mao, C., Lin, L., Wu, J., et al. (2024) Macrophage-Derived GSDMD Promotes Abdominal Aortic Aneurysm and Aortic Smooth Muscle Cells Pyroptosis. International Immunopharmacology, 128, Article ID: 111554.
https://doi.org/10.1016/j.intimp.2024.111554
[49]  Nordon, I.M., Hinchliffe, R.J., Loftus, I.M. and Thompson, M.M. (2010) Pathophysiology and Epidemiology of Abdominal Aortic Aneurysms. Nature Reviews Cardiology, 8, 92-102.
https://doi.org/10.1038/nrcardio.2010.180
[50]  Wang, K., Zhou, Z., Huang, L., Kan, Q., Wang, Z., Wu, W., et al. (2024) PINK1 Dominated Mitochondria Associated Genes Signature Predicts Abdominal Aortic Aneurysm with Metabolic Syndrome. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1870, Article ID: 166919.
https://doi.org/10.1016/j.bbadis.2023.166919
[51]  Golledge, J. (2018) Abdominal Aortic Aneurysm: Update on Pathogenesis and Medical Treatments. Nature Reviews Cardiology, 16, 225-242.
https://doi.org/10.1038/s41569-018-0114-9
[52]  Yuan, Z., Lu, Y., Wei, J., Wu, J., Yang, J. and Cai, Z. (2021) Abdominal Aortic Aneurysm: Roles of Inflammatory Cells. Frontiers in Immunology, 11, Article 609161.
https://doi.org/10.3389/fimmu.2020.609161
[53]  Song, H., Yang, Y., Sun, Y., Wei, G., Zheng, H., Chen, Y., et al. (2022) Circular RNA Cdyl Promotes Abdominal Aortic Aneurysm Formation by Inducing M1 Macrophage Polarization and M1-Type Inflammation. Molecular Therapy, 30, 915-931.
https://doi.org/10.1016/j.ymthe.2021.09.017
[54]  Raffort, J., Lareyre, F., Clément, M., Hassen-Khodja, R., Chinetti, G. and Mallat, Z. (2017) Monocytes and Macrophages in Abdominal Aortic Aneurysm. Nature Reviews Cardiology, 14, 457-471.
https://doi.org/10.1038/nrcardio.2017.52
[55]  Burzyn, D., Kuswanto, W., Kolodin, D., Shadrach, J.L., Cerletti, M., Jang, Y., et al. (2013) A Special Population of Regulatory T Cells Potentiates Muscle Repair. Cell, 155, 1282-1295.
https://doi.org/10.1016/j.cell.2013.10.054
[56]  Juvonen, J., Surcel, H., Satta, J., Teppo, A., Bloigu, A., Syrjälä, H., et al. (1997) Elevated Circulating Levels of Inflammatory Cytokines in Patients with Abdominal Aortic Aneurysm. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 2843-2847.
https://doi.org/10.1161/01.atv.17.11.2843
[57]  Cai, D., Sun, C., Murashita, T., Que, X. and Chen, S. (2023) ADAR1 Non-Editing Function in Macrophage Activation and Abdominal Aortic Aneurysm. Circulation Research, 132, e78-e93.
https://doi.org/10.1161/circresaha.122.321722
[58]  Qin, Z., Bagley, J., Sukhova, G., Baur, W.E., Park, H., Beasley, D., et al. (2015) Angiotensin II-Induced TLR4 Mediated Abdominal Aortic Aneurysm in Apolipoprotein E Knockout Mice Is Dependent on STAT3. Journal of Molecular and Cellular Cardiology, 87, 160-170.
https://doi.org/10.1016/j.yjmcc.2015.08.014
[59]  Dale, M.A., Xiong, W., Carson, J.S., Suh, M.K., Karpisek, A.D., Meisinger, T.M., et al. (2016) Elastin-derived Peptides Promote Abdominal Aortic Aneurysm Formation by Modulating M1/M2 Macrophage Polarization. The Journal of Immunology, 196, 4536-4543.
https://doi.org/10.4049/jimmunol.1502454
[60]  Sánchez-Infantes, D., Nus, M., Navas-Madroñal, M., Fité, J., Pérez, B., Barros-Membrilla, A.J., et al. (2021) Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm. Antioxidants, 10, Article 602.
https://doi.org/10.3390/antiox10040602
[61]  Wang, D., Day, E.A., Townsend, L.K., Djordjevic, D., Jørgensen, S.B. and Steinberg, G.R. (2021) GDF15: Emerging Biology and Therapeutic Applications for Obesity and Cardiometabolic Disease. Nature Reviews Endocrinology, 17, 592-607.
https://doi.org/10.1038/s41574-021-00529-7
[62]  Ferreira, J.P., Packer, M., Butler, J., Filippatos, G., Pocock, S.J., Januzzi, J.L., et al. (2023) Growth Differentiation Factor‐15 and the Effect of Empagliflozin in Heart Failure: Findings from the emperor Program. European Journal of Heart Failure, 26, 155-164.
https://doi.org/10.1002/ejhf.3078
[63]  Itoga, N.K., Rothenberg, K.A., Suarez, P., Ho, T., Mell, M.W., Xu, B., et al. (2019) Metformin Prescription Status and Abdominal Aortic Aneurysm Disease Progression in the U.S. Veteran Population. Journal of Vascular Surgery, 69, 710-716.E3.
https://doi.org/10.1016/j.jvs.2018.06.194
[64]  Raffort, J., Hassen-Khodja, R., Jean-Baptiste, E. and Lareyre, F. (2020) Relationship between Metformin and Abdominal Aortic Aneurysm. Journal of Vascular Surgery, 71, 1056-1062.
https://doi.org/10.1016/j.jvs.2019.08.270
[65]  Hinchliffe, R.J. (2017) Metformin and Abdominal Aortic Aneurysm. European Journal of Vascular and Endovascular Surgery, 54, 679-680.
https://doi.org/10.1016/j.ejvs.2017.08.016
[66]  Zhang, S., Danaei, Z., Bruce, K., Chiu, J.F.M. and Lam, T.K.T. (2023) Acute Activation of GFRAL in the Area Postrema Contributes to Glucose Regulation Independent of Weight. Diabetes, 73, 426-433.
https://doi.org/10.2337/db23-0705
[67]  Kaneto, H., Kimura, T., Obata, A., Shimoda, M. and Kaku, K. (2021) Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History. International Journal of Molecular Sciences, 22, Article 2596.
https://doi.org/10.3390/ijms22052596
[68]  Natali, A., Nesti, L., Venturi, E., Shore, A.C., Khan, F., Gooding, K., et al. (2018) Metformin Is the Key Factor in Elevated Plasma Growth Differentiation Factor‐15 Levels in Type 2 Diabetes: A Nested, Case-Control Study. Diabetes, Obesity and Metabolism, 21, 412-416.
https://doi.org/10.1111/dom.13519
[69]  Li, H., Tang, D., Chen, J., Hu, Y., Cai, X. and Zhang, P. (2021) The Clinical Value of GDF15 and Its Prospective Mechanism in Sepsis. Frontiers in Immunology, 12, Article 710977.
https://doi.org/10.3389/fimmu.2021.710977

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