This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

Accuscript Consultancy Ludhiana India

Department of Pathological Physiology Faculty of Medicine and Dentistry Palacky University Olomouc Czechia

Departments of Experimental Medicine and Immunology University Hospital Olomouc Olomouc Czechia

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Czechia

Zobrazit více v PubMed

Martinez FJ, Collard HR, Pardo A, Raghu G, Richeldi L, Selman M, et al. . Idiopathic Pulmonary Fibrosis. Nat Rev Dis Primers (2017) 3:17074.  10.1038/nrdp.2017.74 PubMed DOI

Pardo A, Selman M. The Interplay of the Genetic Architecture, Aging, and Environmental Factors in the Pathogenesis of Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol (2021) 64(2):163–72.  10.1165/rcmb.2020-0373PS PubMed DOI

Barros A, Oldham J, Noth I. Genetics of Idiopathic Pulmonary Fibrosis. Am J Med Sci (2019) 357(5):379–83.  10.1016/j.amjms.2019.02.009 PubMed DOI PMC

Kishore A, Zizkova V, Kocourkova L, Petrek M. A Dataset of 26 Candidate Gene and Pro-Inflammatory Cytokine Variants for Association Studies in Idiopathic Pulmonary Fibrosis: Frequency Distribution in Normal Czech Population. Front Immunol (2015) 6:476.  10.3389/fimmu.2015.00476 PubMed DOI PMC

Kishore A, Borucka J, Petrkova J, Petrek M. Novel Insights Into miRNA in Lung and Heart Inflammatory Diseases. Mediators Inflamm (2014) 2014:259131.  10.1155/2014/259131 PubMed DOI PMC

Kishore A, Zizkova V, Kocourkova L, Petrkova J, Bouros E, Nunes H, et al. . Association Study for 26 Candidate Loci in Idiopathic Pulmonary Fibrosis Patients From Four European Populations. Front Immunol (2016) 7:274.  10.3389/fimmu.2016.00274 PubMed DOI PMC

Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, et al. . Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med (2020) 201(5):564–74.  10.1164/rccm.201905-1017OC PubMed DOI PMC

Vasse GF, Nizamoglu M, Heijink IH, Schleputz M, van Rijn P, Thomas MJ, et al. . Macrophage-Stroma Interactions in Fibrosis: Biochemical, Biophysical, and Cellular Perspectives. J Pathol (2021) 254(4):344–57.  10.1002/path.5632 PubMed DOI PMC

Perciani CT, MacParland SA. Lifting the Veil on Macrophage Diversity in Tissue Regeneration and Fibrosis. Sci Immunol (2019) 4(40):eaaz0749.  10.1126/sciimmunol.aaz0749 PubMed DOI

Tarique AA, Logan J, Thomas E, Holt PG, Sly PD, Fantino E. Phenotypic, Functional, and Plasticity Features of Classical and Alternatively Activated Human Macrophages. Am J Respir Cell Mol Biol (2015) 53(5):676–88.  10.1165/rcmb.2015-0012OC PubMed DOI

Bart VMT, Pickering RJ, Taylor PR, Ipseiz N. Macrophage Reprogramming for Therapy. Immunology (2020) 163(2):128–44.  10.1111/imm.13300 PubMed DOI PMC

Porcheray F, Viaud S, Rimaniol AC, Leone C, Samah B, Dereuddre-Bosquet N, et al. . Macrophage Activation Switching: An Asset for the Resolution of Inflammation. Clin Exp Immunol (2005) 142(3):481–9.  10.1111/j.1365-2249.2005.02934.x PubMed DOI PMC

Kudlik G, Hegyi B, Czibula A, Monostori E, Buday L, Uher F. Mesenchymal Stem Cells Promote Macrophage Polarization Toward M2b-Like Cells. Exp Cell Res (2016) 348(1):36–45.  10.1016/j.yexcr.2016.08.022 PubMed DOI

Gharib SA, McMahan RS, Eddy WE, Long ME, Parks WC, Aitken ML, et al. . Transcriptional and Functional Diversity of Human Macrophage Repolarization. J Allergy Clin Immunol (2019) 143(4):1536–48.  10.1016/j.jaci.2018.10.046 PubMed DOI PMC

Wang LX, Zhang SX, Wu HJ, Rong XL, Guo J. M2b Macrophage Polarization and Its Roles in Diseases. J Leukoc Biol (2019) 106(2):345–58.  10.1002/JLB.3RU1018-378RR PubMed DOI PMC

Liu G, Zhai H, Zhang T, Li S, Li N, Chen J, et al. . New Therapeutic Strategies for IPF: Based on the “Phagocytosis-Secretion-Immunization” Network Regulation Mechanism of Pulmonary Macrophages. BioMed Pharmacother (2019) 118:109230.  10.1016/j.biopha.2019.109230 PubMed DOI

Lee KY. M1 and M2 Polarization of Macrophages: A Mini-Review. Med Biol Sci Eng (2019) 2(1):1–5.  10.30579/mbse.2019.2.1.1 DOI

Murray PJ. Macrophage Polarization. Annu Rev Physiol (2017) 79:541–66.  10.1146/annurev-physiol-022516-034339 PubMed DOI

Mantovani A, Locati M. Tumor-Associated Macrophages as a Paradigm of Macrophage Plasticity, Diversity, and Polarization: Lessons and Open Questions. Arterioscler Thromb Vasc Biol (2013) 33(7):1478–83.  10.1161/ATVBAHA.113.300168 PubMed DOI

Maccio A, Gramignano G, Cherchi MC, Tanca L, Melis L, Madeddu C. Role of M1-Polarized Tumor-Associated Macrophages in the Prognosis of Advanced Ovarian Cancer Patients. Sci Rep (2020) 10(1):6096.  10.1038/s41598-020-63276-1 PubMed DOI PMC

Zhang M, He Y, Sun X, Li Q, Wang W, Zhao A, et al. . A High M1/M2 Ratio of Tumor-Associated Macrophages Is Associated With Extended Survival in Ovarian Cancer Patients. J Ovarian Res (2014) 7:19.  10.1186/1757-2215-7-19 PubMed DOI PMC

Suarez-Arriaga MC, Mendez-Tenorio A, Perez-Koldenkova V, Fuentes-Panana EM. Claudin-Low Breast Cancer Inflammatory Signatures Support Polarization of M1-Like Macrophages With Protumoral Activity. Cancers (Basel) (2021) 13(9):2248.  10.3390/cancers13092248 PubMed DOI PMC

Goda C, Balli D, Black M, Milewski D, Le T, Ustiyan V, et al. . Loss of FOXM1 in Macrophages Promotes Pulmonary Fibrosis by Activating P38 MAPK Signaling Pathway. PloS Genet (2020) 16(4):e1008692.  10.1371/journal.pgen.1008692 PubMed DOI PMC

Byrne AJ, Maher TM, Lloyd CM. Pulmonary Macrophages: A New Therapeutic Pathway in Fibrosing Lung Disease? Trends Mol Med (2016) 22(4):303–16.  10.1016/j.molmed.2016.02.004 PubMed DOI

Zhang L, Wang Y, Wu G, Xiong W, Gu W, Wang CY. Macrophages: Friend or Foe in Idiopathic Pulmonary Fibrosis? Respir Res (2018) 19(1):170.  10.1186/s12931-018-0864-2 PubMed DOI PMC

Wojtan P, Mierzejewski M, Osinska I, Domagala-Kulawik J. Macrophage Polarization in Interstitial Lung Diseases. Cent Eur J Immunol (2016) 41(2):159–64.  10.5114/ceji.2016.60990 PubMed DOI PMC

Byrne AJ, Mathie SA, Gregory LG, Lloyd CM. Pulmonary Macrophages: Key Players in the Innate Defence of the Airways. Thorax (2015) 70(12):1189–96.  10.1136/thoraxjnl-2015-207020 PubMed DOI

Gharib SA, Johnston LK, Huizar I, Birkland TP, Hanson J, Wang Y, et al. . MMP28 Promotes Macrophage Polarization Toward M2 Cells and Augments Pulmonary Fibrosis. J Leukoc Biol (2014) 95(1):9–18.  10.1189/jlb.1112587 PubMed DOI PMC

Medbury HJ, James V, Ngo J, Hitos K, Wang Y, Harris DC, et al. . Differing Association of Macrophage Subsets With Atherosclerotic Plaque Stability. Int Angiol (2013) 32(1):74–84. PubMed

Polverino F, Balestro E, Spagnolo P. Clinical Presentations, Pathogenesis, and Therapy of Sarcoidosis: State of the Art. J Clin Med (2020) 9(8):2363.  10.3390/jcm9082363 PubMed DOI PMC

Shamaei M, Mortaz E, Pourabdollah M, Garssen J, Tabarsi P, Velayati A, et al. . Evidence for M2 Macrophages in Granulomas From Pulmonary Sarcoidosis: A New Aspect of Macrophage Heterogeneity. Hum Immunol (2018) 79(1):63–9.  10.1016/j.humimm.2017.10.009 PubMed DOI

Partida-Zavala N, Antonio Ponce-Gallegos M, Buendia-Roldan I, Falfan-Valencia R. Type 2 Macrophages and Th2 CD4+ Cells in Interstitial Lung Diseases (ILDs): An Overview. Sarcoidosis Vasc Diffuse Lung Dis (2018) 35(2):98–108.  10.36141/svdld.v35i2.6691 PubMed DOI PMC

Guo Z, Li S, Zhang N, Kang Q, Zhai H. Schisandra Inhibit Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rats via Suppressing M2 Macrophage Polarization. BioMed Res Int (2020) 2020:5137349.  10.1155/2020/5137349 PubMed DOI PMC

Wang J, Xu L, Xiang Z, Ren Y, Zheng X, Zhao Q, et al. . Microcystin-LR Ameliorates Pulmonary Fibrosis via Modulating CD206(+) M2-Like Macrophage Polarization. Cell Death Dis (2020) 11(2):136.  10.1038/s41419-020-2329-z PubMed DOI PMC

Pan T, Zhou Q, Miao K, Zhang L, Wu G, Yu J, et al. . Suppressing Sart1 to Modulate Macrophage Polarization by siRNA-Loaded Liposomes: A Promising Therapeutic Strategy for Pulmonary Fibrosis. Theranostics (2021) 11(3):1192–206.  10.7150/thno.48152 PubMed DOI PMC

Guo J, Fang Y, Jiang F, Li L, Zhou H, Xu X, et al. . Neohesperidin Inhibits TGF-Beta1/Smad3 Signaling and Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice. Eur J Pharmacol (2019) 864:172712.  10.1016/j.ejphar.2019.172712 PubMed DOI

Lv Q, Wang J, Xu C, Huang X, Ruan Z, Dai Y. Pirfenidone Alleviates Pulmonary Fibrosis In Vitro and In Vivo Through Regulating Wnt/GSK-3beta/Beta-Catenin and TGF-Beta1/Smad2/3 Signaling Pathways. Mol Med (2020) 26(1):49.  10.1186/s10020-020-00173-3 PubMed DOI PMC

Wang P, Nie X, Wang Y, Li Y, Ge C, Zhang L, et al. . Multiwall Carbon Nanotubes Mediate Macrophage Activation and Promote Pulmonary Fibrosis Through TGF-Beta/Smad Signaling Pathway. Small (2013) 9(22):3799–811.  10.1002/smll.201300607 PubMed DOI

Zhu L, Fu X, Chen X, Han X, Dong P. M2 Macrophages Induce EMT Through the TGF-Beta/Smad2 Signaling Pathway. Cell Biol Int (2017) 41(9):960–8.  10.1002/cbin.10788 PubMed DOI

Hou J, Shi J, Chen L, Lv Z, Chen X, Cao H, et al. . M2 Macrophages Promote Myofibroblast Differentiation of LR-MSCs and are Associated With Pulmonary Fibrogenesis. Cell Commun Signal (2018) 16(1):89.  10.1186/s12964-018-0300-8 PubMed DOI PMC

Okazaki H, Sato S, Koyama K, Morizumi S, Abe S, Azuma M, et al. . The Novel Inhibitor PRI-724 for Wnt/beta-Catenin/CBP Signaling Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice. Exp Lung Res (2019) 45(7):188–99.  10.1080/01902148.2019.1638466 PubMed DOI

Cao H, Wang C, Chen X, Hou J, Xiang Z, Shen Y, et al. . Inhibition of Wnt/beta-Catenin Signaling Suppresses Myofibroblast Differentiation of Lung Resident Mesenchymal Stem Cells and Pulmonary Fibrosis. Sci Rep (2018) 8(1):13644.  10.1038/s41598-018-28968-9 PubMed DOI PMC

Guo X, Li T, Xu Y, Xu X, Zhu Z, Zhang Y, et al. . Increased Levels of Gab1 and Gab2 Adaptor Proteins Skew Interleukin-4 (IL-4) Signaling Toward M2 Macrophage-Driven Pulmonary Fibrosis in Mice. J Biol Chem (2017) 292(34):14003–15.  10.1074/jbc.M117.802066 PubMed DOI PMC

Zhao J, Okamoto Y, Asano Y, Ishimaru K, Aki S, Yoshioka K, et al. . Sphingosine-1-Phosphate Receptor-2 Facilitates Pulmonary Fibrosis Through Potentiating IL-13 Pathway in Macrophages. PloS One (2018) 13(5):e0197604.  10.1371/journal.pone.0197604 PubMed DOI PMC

Migliaccio CT, Buford MC, Jessop F, Holian A. The IL-4Ralpha Pathway in Macrophages and Its Potential Role in Silica-Induced Pulmonary Fibrosis. J Leukoc Biol (2008) 83(3):630–9.  10.1189/jlb.0807533 PubMed DOI

Sennello JA, Misharin AV, Flozak AS, Berdnikovs S, Cheresh P, Varga J, et al. . Lrp5/beta-Catenin Signaling Controls Lung Macrophage Differentiation and Inhibits Resolution of Fibrosis. Am J Respir Cell Mol Biol (2017) 56(2):191–201.  10.1165/rcmb.2016-0147OC PubMed DOI PMC

Zhang N, Yang K, Bai J, Yi J, Gao C, Zhao J, et al. . Myeloid-Specific Blockade of Notch Signaling Alleviates Murine Pulmonary Fibrosis Through Regulating Monocyte-Derived Ly6c(lo) MHCII(hi) Alveolar Macrophages Recruitment and TGF-Beta Secretion. FASEB J (2020) 34(8):11168–84.  10.1096/fj.201903086RR PubMed DOI

Han B, Chu C, Su X, Zhang N, Zhou L, Zhang M, et al. . N(6)-Methyladenosine-Dependent Primary microRNA-126 Processing Activated PI3K-AKT-mTOR Pathway Drove the Development of Pulmonary Fibrosis Induced by Nanoscale Carbon Black Particles in Rats. Nanotoxicology (2020) 14(1):1–20.  10.1080/17435390.2019.1661041 PubMed DOI

Tsitoura E, Wells AU, Karagiannis K, Lasithiotaki I, Vasarmidi E, Bibaki E, et al. . MiR-185/AKT and miR-29a/Collagen 1a Pathways Are Activated in IPF BAL Cells. Oncotarget (2016) 7(46):74569–81.  10.18632/oncotarget.12740 PubMed DOI PMC

Haydar D, Cory TJ, Birket SE, Murphy BS, Pennypacker KR, Sinai AP, et al. . Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-kappaB Signaling Pathways. J Immunol (2019) 203(4):1021–30.  10.4049/jimmunol.1801228 PubMed DOI PMC

Chung EJ, Kwon S, Reedy JL, White AO, Song JS, Hwang I, et al. . IGF-1 Receptor Signaling Regulates Type II Pneumocyte Senescence and Resulting Macrophage Polarization in Lung Fibrosis. Int J Radiat Oncol Biol Phys (2021) 110(2):526–38.  10.1016/j.ijrobp.2020.12.035 PubMed DOI PMC

Lu Y, Li C, Du S, Chen X, Zeng X, Liu F, et al. . 4-1bb Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice. Front Immunol (2018) 9:1848.  10.3389/fimmu.2018.01848 PubMed DOI PMC

Vermeulen Z, Hervent AS, Dugaucquier L, Vandekerckhove L, Rombouts M, Beyens M, et al. . Inhibitory Actions of the NRG-1/ErbB4 Pathway in Macrophages During Tissue Fibrosis in the Heart, Skin, and Lung. Am J Physiol Heart Circ Physiol (2017) 313(5):H934–H45.  10.1152/ajpheart.00206.2017 PubMed DOI

Joshi N, Watanabe S, Verma R, Jablonski RP, Chen CI, Cheresh P, et al. . A Spatially Restricted Fibrotic Niche in Pulmonary Fibrosis Is Sustained by M-CSF/M-CSFR Signalling in Monocyte-Derived Alveolar Macrophages. Eur Respir J (2020) 55(1):1900646.  10.1183/13993003.00646-2019 PubMed DOI PMC

Kishore A, Navratilova Z, Kolek V, Novosadova E, Cepe K, du Bois RM, et al. . Expression Analysis of Extracellular microRNA in Bronchoalveolar Lavage Fluid From Patients With Pulmonary Sarcoidosis. Respirology (2018) 23(12):1166–72.  10.1111/resp.13364 PubMed DOI

Self-Fordham JB, Naqvi AR, Uttamani JR, Kulkarni V, Nares S. MicroRNA: Dynamic Regulators of Macrophage Polarization and Plasticity. Front Immunol (2017) 8:1062.  10.3389/fimmu.2017.01062 PubMed DOI PMC

Essandoh K, Li Y, Huo J, Fan GC. MiRNA-Mediated Macrophage Polarization and Its Potential Role in the Regulation of Inflammatory Response. Shock (2016) 46(2):122–31.  10.1097/SHK.0000000000000604 PubMed DOI PMC

Liu G, Abraham E. MicroRNAs in Immune Response and Macrophage Polarization. Arterioscler Thromb Vasc Biol (2013) 33(2):170–7.  10.1161/ATVBAHA.112.300068 PubMed DOI PMC

Wu XQ, Dai Y, Yang Y, Huang C, Meng XM, Wu BM, et al. . Emerging Role of microRNAs in Regulating Macrophage Activation and Polarization in Immune Response and Inflammation. Immunology (2016) 148(3):237–48.  10.1111/imm.12608 PubMed DOI PMC

Zhu D, Pan C, Li L, Bian Z, Lv Z, Shi L, et al. . MicroRNA-17/20a/106a Modulate Macrophage Inflammatory Responses Through Targeting Signal-Regulatory Protein Alpha. J Allergy Clin Immunol (2013) 132(2):426–36 e8.  10.1016/j.jaci.2013.02.005 PubMed DOI PMC

Barna BP, McPeek M, Malur A, Fessler MB, Wingard CJ, Dobbs L, et al. . Elevated MicroRNA-33 in Sarcoidosis and a Carbon Nanotube Model of Chronic Granulomatous Disease. Am J Respir Cell Mol Biol (2016) 54(6):865–71.  10.1165/rcmb.2015-0332OC PubMed DOI PMC

Khan MJ, Singh P, Dohare R, Jha R, Rahmani AH, Almatroodi SA, et al. . Inhibition of miRNA-34a Promotes M2 Macrophage Polarization and Improves LPS-Induced Lung Injury by Targeting Klf4. Genes (Basel) (2020) 11(9):966.  10.3390/genes11090966 PubMed DOI PMC

Eissa MG, Artlett CM. The MicroRNA miR-155 Is Essential in Fibrosis. Noncoding RNA (2019) 5(1):23.  10.3390/ncrna5010023 PubMed DOI PMC

Jaiswal A, Maurya M, Maurya P, Barthwal MK. Lin28B Regulates Angiotensin II-Mediated Let-7c/miR-99a MicroRNA Formation Consequently Affecting Macrophage Polarization and Allergic Inflammation. Inflammation (2020) 43(5):1846–61.  10.1007/s10753-020-01258-1 PubMed DOI

Arora S, Dev K, Agarwal B, Das P, Syed MA. Macrophages: Their Role, Activation and Polarization in Pulmonary Diseases. Immunobiology (2018) 223(4-5):383–96.  10.1016/j.imbio.2017.11.001 PubMed DOI PMC

Liang Y, Xie J, Che D, Zhang C, Lin Y, Feng L, et al. . MiR-124-3p Helps to Protect Against Acute Respiratory Distress Syndrome by Targeting P65. Biosci Rep (2020) 40(5):BSR20192132.  10.1042/BSR20192132 PubMed DOI PMC

Shi J, Chen M, Ouyang L, Wang Q, Guo Y, Huang L, et al. . miR-142-5p and miR-130a-3p Regulate Pulmonary Macrophage Polarization and Asthma Airway Remodeling. Immunol Cell Biol (2020) 98(9):715–25.  10.1111/imcb.12369 PubMed DOI

Huang C, Liu XJ, Zhou Q, Xie J, Ma TT, Meng XM, et al. . MiR-146a Modulates Macrophage Polarization by Inhibiting Notch1 Pathway in RAW264. 7 Macrophages Int Immunopharmacol (2016) 32:46–54.  10.1016/j.intimp.2016.01.009 PubMed DOI

Novosadova E, Chabronova A, Kolek V, Petrek M, Navratilova Z. The Serum Expression of Selected miRNAs in Pulmonary Sarcoidosis With/Without Lofgren’s Syndrome. Mediators Inflamm (2016) 2016:1246129.  10.1155/2016/1246129 PubMed DOI PMC

Pirlog R, Cismaru A, Nutu A, Berindan-Neagoe I. Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization. Int J Mol Sci (2021) 22(2):746.  10.3390/ijms22020746 PubMed DOI PMC

Banerjee S, Xie N, Cui H, Tan Z, Yang S, Icyuz M, et al. . MicroRNA Let-7c Regulates Macrophage Polarization. J Immunol (2013) 190(12):6542–9.  10.4049/jimmunol.1202496 PubMed DOI PMC

Duru N, Wolfson B, Zhou Q. Mechanisms of the Alternative Activation of Macrophages and non-Coding RNAs in the Development of Radiation-Induced Lung Fibrosis. World J Biol Chem (2016) 7(4):231–9.  10.4331/wjbc.v7.i4.231 PubMed DOI PMC

Su S, Zhao Q, He C, Huang D, Liu J, Chen F, et al. . miR-142-5p and miR-130a-3p are Regulated by IL-4 and IL-13 and Control Profibrogenic Macrophage Program. Nat Commun (2015) 6:8523.  10.1038/ncomms9523 PubMed DOI PMC

Wang W, Liu Z, Su J, Chen WS, Wang XW, Bai SX, et al. . Macrophage Micro-RNA-155 Promotes Lipopolysaccharide-Induced Acute Lung Injury in Mice and Rats. Am J Physiol Lung Cell Mol Physiol (2016) 311(2):L494–506.  10.1152/ajplung.00001.2016 PubMed DOI

Kurowska-Stolarska M, Hasoo MK, Welsh DJ, Stewart L, McIntyre D, Morton BE, et al. . The Role of microRNA-155/Liver X Receptor Pathway in Experimental and Idiopathic Pulmonary Fibrosis. J Allergy Clin Immunol (2017) 139(6):1946–56.  10.1016/j.jaci.2016.09.021 PubMed DOI PMC

Duru N, Zhang Y, Gernapudi R, Wolfson B, Lo PK, Yao Y, et al. . Loss of miR-140 Is a Key Risk Factor for Radiation-Induced Lung Fibrosis Through Reprogramming Fibroblasts and Macrophages. Sci Rep (2016) 6:39572.  10.1038/srep39572 PubMed DOI PMC

Zhou D, Wu Y, Wang S, Li J, Luan J. Harnessing Noncoding RNA-Based Macrophage Polarization: Emerging Therapeutic Opportunities for Fibrosis. Immun Inflamm Dis (2020) 8(4):793–806.  10.1002/iid3.341 PubMed DOI PMC

Yao MY, Zhang WH, Ma WT, Liu QH, Xing LH, Zhao GF. microRNA-328 in Exosomes Derived From M2 Macrophages Exerts a Promotive Effect on the Progression of Pulmonary Fibrosis via FAM13A in a Rat Model. Exp Mol Med (2019) 51(6):1–16.  10.1038/s12276-019-0255-x PubMed DOI PMC

Guiot J, Cambier M, Boeckx A, Henket M, Nivelles O, Gester F, et al. . Macrophage-Derived Exosomes Attenuate Fibrosis in Airway Epithelial Cells Through Delivery of Antifibrotic miR-142-3p. Thorax (2020) 75(10):870–81.  10.1136/thoraxjnl-2019-214077 PubMed DOI PMC

Lee H, Groot M, Pinilla-Vera M, Fredenburgh LE, Jin Y. Identification of miRNA-Rich Vesicles in Bronchoalveolar Lavage Fluid: Insights Into the Function and Heterogeneity of Extracellular Vesicles. J Control Release (2019) 294:43–52.  10.1016/j.jconrel.2018.12.008 PubMed DOI PMC

Huang R, Qin C, Wang J, Hu Y, Zheng G, Qiu G, et al. . Differential Effects of Extracellular Vesicles From Aging and Young Mesenchymal Stem Cells in Acute Lung Injury. Aging (Albany NY) (2019) 11(18):7996–8014.  10.18632/aging.102314 PubMed DOI PMC

Xiao T, Zou Z, Xue J, Syed BM, Sun J, Dai X, et al. . LncRNA H19-Mediated M2 Polarization of Macrophages Promotes Myofibroblast Differentiation in Pulmonary Fibrosis Induced by Arsenic Exposure. Environ Pollut (2021) 268(Pt A):115810.  10.1016/j.envpol.2020.115810 PubMed DOI

Wang R, Xu B. TGF-Beta1-Modified MSC-Derived Exosomal miR-135b Attenuates Cartilage Injury via Promoting M2 Synovial Macrophage Polarization by Targeting MAPK6. Cell Tissue Res (2021) 384(1):113–27.  10.1007/s00441-020-03319-1 PubMed DOI

Mechanisms and Effects of Macrophage Polarization and Its Specifics in Pulmonary Environment

High aspect ratio nanomaterial-induced macrophage polarization is mediated by changes in miRNA levels