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Macrophage polarization in intestinal inflammation and gut homeostasis

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Abstract

Gut homeostasis is a process that requires a prudent balance of host responses to the beneficial enteric microbial community and the pathogenic stimuli that can arise. The lack of this balance in the intestine can result in inflammatory bowel diseases, where the immune system dysfunctions leading to exacerbated inflammatory responses. In this process, macrophages are considered to play a pivotal role. In this review, we describe the important role of macrophages in maintaining intestinal homeostasis and we discuss how altered macrophage function may lead to inflammatory bowel diseases. The plasticity of macrophages during the gut inflammatory response shows the broad role of these cells in orchestrating not only the onset of inflammation but also its termination as well as healing and repair. Indeed, the state of macrophage polarization can be the key factor in defining the resolution or the progression of inflammation and disease. Here, we discuss the different populations of macrophages and their implication in development, propagation, control and resolution of inflammatory bowel diseases.

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References

  1. Gordon S, Crocker PR, Morris L, Lee SH, Perry VH, Hume DA. Localization and function of tissue macrophages. Biochem macrophages. Chichester: John Wiley & Sons Ltd.; 1986. p. 54–67.

    Google Scholar 

  2. Matzinger P. Tolerance, danger, and the extended family. Annu Rev lmmunol. 1994;12:991–1045.

    CAS  Google Scholar 

  3. Janeway CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54:1–13.

    CAS  PubMed  Google Scholar 

  4. Fearon DT, Locksley RM. The instructive role of innate immunity in the acquired immune response. Elem Immun. 1996;272:50–4.

    CAS  Google Scholar 

  5. Silverstein SC. Phagocytosis of microbes: insights and prospects. Trends Cell Biol. 1995;5:141–2.

    CAS  PubMed  Google Scholar 

  6. Allen L-AH, Aderem A. Mechanisms of phagocytosis. Curr Opin Immunol. 1996;8:36–40.

    CAS  PubMed  Google Scholar 

  7. Zhang X, Mosser DM. Macrophage activation by endogenous danger signals. J Pathol. 2008;214:161–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Metschnikoff E. Ueber den Kampf der Zellen gegen Erysipel-kokken-Ein Beitrag zur Phagocytenlehre. Arch für Pathol Anat Physiol für Klin Med. 1887;107:209–49.

    Google Scholar 

  9. Tauber AI. Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol. 2003;4:897–901.

    CAS  PubMed  Google Scholar 

  10. Varol C, Mildner A, Jung S. Macrophages: development and tissue specialization. Annu Rev Immunol. 2015. https://doi.org/10.1146/annurev-immunol-032414-112220.

    Article  PubMed  Google Scholar 

  11. Platt AM, Mowat AMI. Mucosal macrophages and the regulation of immune responses in the intestine. Immunol Lett. 2008;119:22–31.

    CAS  PubMed  Google Scholar 

  12. Grainger JR, Konkel JE, Zangerle-Murray T, Shaw TN. Macrophages in gastrointestinal homeostasis and inflammation. Pflugers Arch Eur J Physiol. 2017;469:527–39.

    CAS  Google Scholar 

  13. Gren ST, Grip O. Role of monocytes and intestinal macrophages in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2016;22:1992–8.

    PubMed  Google Scholar 

  14. Lissner D, Schumann M, Batra A, Kredel L-I, Kühl AA, Erben U, et al. Monocyte and M1 macrophage-induced barrier defect contributes to chronic intestinal inflammation in IBD. Inflamm Bowel Dis. 2015;21:1297–305.

    PubMed  Google Scholar 

  15. Podolsky DK. Inflammatory Bowel disease. N Engl J Med. 1991;325:928–37. https://doi.org/10.1056/NEJM199309303291401.

    Article  CAS  PubMed  Google Scholar 

  16. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.

    CAS  PubMed  Google Scholar 

  17. Graff LA, Walker JR, Bernstein CN. Depression and anxiety in iflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis. 2009;15:1105–18.

    PubMed  Google Scholar 

  18. Jung HC, Eckmann L, Yang SK, Panja A, Fierer J, Morzycka-Wroblewska E, et al. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest. 1995;95:55–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14:141–53.

    CAS  PubMed  Google Scholar 

  20. Pull SL, Doherty JM, Mills JC, Gordon JI, Stappenbeck TS. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc Natl Acad Sci USA. 2005;102:99–104.

    CAS  PubMed  Google Scholar 

  21. Yan F, Wang L, Shi Y, Cao H, Liu L, Washington MK, et al. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. AJP Gastrointest Liver Physiol. 2012;302:G504–G514514. https://doi.org/10.1152/ajpgi.00312.2011.

    Article  CAS  Google Scholar 

  22. Salim SY, Söderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17:362–81.

    PubMed  Google Scholar 

  23. Seo DH, Che X, Kwak MS, Kim S, Kim JH, Ma HW, et al. Interleukin-33 regulates intestinal inflammation by modulating macrophages in inflammatory bowel disease. Sci Rep. 2017. https://doi.org/10.1038/s41598-017-00840-2.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121–41. https://doi.org/10.1016/j.cell.2014.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nagashima R, Maeda K, Imai Y, Takahashi T. Lamina propria macrophages in the human gastrointestinal mucosa: their distribution, immunohistological phenotype, and function. J Histochem Cytochem. 1996;44:721–31.

    CAS  PubMed  Google Scholar 

  26. Nikolaus S, Bauditz J, Gionchetti P, Witt C, Lochs H, Schreiber S. Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation. Gut. 1998;42:470–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Powell N, Walker AW, Stolarczyk E, Canavan JB, Gökmen MR, Marks E, et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid Cells. Immunity. 2012;37:674–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Maloy KJ, Kullberg MC. IL-23 and Th17 cytokines in intestinal homeostasis. Mucosal Immunol. 2008;1:339–49.

    CAS  PubMed  Google Scholar 

  29. Gerlach K, Hwang Y, Nikolaev A, Atreya R, Dornhoff H, Steiner S, et al. T H 9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol. 2014;15:676–86.

    CAS  PubMed  Google Scholar 

  30. Schmidt A, Oberle N, Krammer PH. Molecular mechanisms oftreg-mediatedt cell suppression. Front Immunol. 2012. https://doi.org/10.3389/fimmu.2012.00051.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev. 2006;212:28–50.

    CAS  PubMed  Google Scholar 

  32. Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T, et al. A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice. Cell Host Microbe. 2013;13:711–22. https://doi.org/10.1016/j.chom.2013.05.013.

    Article  CAS  PubMed  Google Scholar 

  33. Anderson P, Souza-Moreira L, Morell M, Caro M, O’Valle F, Gonzalez-Rey E, et al. Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis. Gut. 2013;62:1131–41.

    CAS  PubMed  Google Scholar 

  34. Kozicky LK, Menzies SC, Hotte N, Madsen KL, Sly LM. Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10 production. Eur J Immunol. 2019. https://doi.org/10.1002/eji.201848014.

    Article  PubMed  Google Scholar 

  35. Tiemessen MM, Jagger AL, Evans HG, Van Herwijnen MJC, John S, Taams LS. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci. 2007;104:19446–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Mackaness GB. Cellular Immunity and the parasite. Adv Exp Med Biol. 1977;93:65–73.

    CAS  PubMed  Google Scholar 

  38. Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014;6:1–13.

    CAS  Google Scholar 

  39. 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. https://doi.org/10.1016/j.immuni.2014.06.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Murray HW, Spitalny GL, Nathan CF. Activation of mouse peritoneal macrophages in vitro and in vivo by interferon-gamma. J Immunol. 1985;134:1619–22.

    CAS  PubMed  Google Scholar 

  41. Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3:23–35.

    CAS  PubMed  Google Scholar 

  42. Stein M, SK, Harris N, Gordon S, Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med. 1992;176:287–92.

    CAS  PubMed  Google Scholar 

  43. Sutterwala BFS, Noel GJ, Salgame P, Mosser DM. Macrophage Fcg receptor Type I. J Exp Med. 1998;188:217–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Fleming BD, Mosser DM. Regulatory macrophages: setting the threshold for therapy. Eur J Immunol. 2011;41:2498–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Gerber JS, Mosser DM. Reversing lipopolysaccharide toxicity by ligating the macrophage Fcγ receptors. J Immunol. 2001;166:6861–8.

    CAS  PubMed  Google Scholar 

  46. Mosser DM. The many faces of macrophage activation. J Leukoc Biol. 2003;73:209–12.

    CAS  PubMed  Google Scholar 

  47. Mosser DM, Gonçalves R. Activation of murine macrophages. Curr Protoc Immunol. 2015. https://doi.org/10.1002/0471142735.im1402s111.

    Article  Google Scholar 

  48. Bull DM, Bookman MA. Isolation and functional characterization of human intestinal mucosal lymphoid cells. J Clin Invest. 1977;59:966–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Hume DA, Loutit JF, Gordon S. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of bone and associated connective tissue. J Cell Sci. 1984;66:189–94.

    CAS  PubMed  Google Scholar 

  50. Lee SH, Starkey PM, Gordon S. Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80. J Exp Med. 1985;161:475–89.

    CAS  PubMed  Google Scholar 

  51. Bain CC, Bravo-Blas A, Scott CL, Gomez Perdiguero E, Geissmann F, Henri S, et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol. 2014;15:929–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. De Schepper S, Verheijden S, Aguilera-Lizarraga J, Viola MF, Boesmans W, Stakenborg N, et al. Self-maintaining gut macrophages are essential for intestinal homeostasis. Cell. 2018;175(400–415):e13.

    Google Scholar 

  53. Shaw TN, Houston SA, Wemyss K, Bridgeman HM, Barbera TA, Zangerle-Murray T, et al. Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression. J Exp Med. 2018;215:1507–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Bain CC, Mowat AMI. Macrophages in gastrointestinal homeostasis and inflammation. Immunol Rev. 2014;260:102–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Bain CC, Scott CL, Uronen-Hansson H, Gudjonsson S, Jansson O, Grip O, et al. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C hi monocyte precursors. Mucosal Immunol. 2013;6:498–510.

    CAS  PubMed  Google Scholar 

  56. Hirotani T, Lee PY, Kuwata H, Yamamoto M, Matsumoto M, Kawase I, et al. The nuclear IκB protein IκBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria. J Immunol. 2005;174:3650–7.

    CAS  PubMed  Google Scholar 

  57. Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Kronenberg M. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10:1178–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 2013;229:176–85.

    CAS  PubMed  Google Scholar 

  59. Gordon S, Pluddemann A, Martinez EF. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014;262:36–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Eckmann L, Kagnoff MF, Fierer J. Epithelial cells secrete the chemokine interleukin-8 in response to bacterial entry. Infect Immun. 1993;61:4569–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Reinecker HC, Loh EY, Ringler DJ, Mehta A, Rombeau JL, MacDermott RP. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology. 1995;108:40–50.

    CAS  PubMed  Google Scholar 

  62. Grimm M, Pullman W, Bennett G, Sullivan P, Pavli P, Doe W. Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa. J Gastroenterol Hepatol. 1995;10:387–95.

    CAS  PubMed  Google Scholar 

  63. Platt AM, Bain CC, Bordon Y, Sester DP, Mowat AM. An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J Immunol. 2010;184:6843–54.

    CAS  PubMed  Google Scholar 

  64. Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2000;6:21–33.

    CAS  PubMed  Google Scholar 

  65. Sperber K, Ogata S, Sylvester C, Aisenberg J, Chen A, Mayer L, et al. A novel human macrophage-derived intestinal mucin secretagogue: implications for the pathogenesis of inflammatory bowel disease. Gastroenterology. 1993;104:1302–9.

    CAS  PubMed  Google Scholar 

  66. Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, Friedlander G, et al. Ly6Chi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity. 2012;37:1076–90. https://doi.org/10.1016/j.immuni.2012.08.026.

    Article  CAS  PubMed  Google Scholar 

  67. Schwarzmaier D, Foell D, Weinhage T, Varga G, Däbritz J. Peripheral monocyte functions and activation in patients with quiescent Crohn’s disease. PLoS ONE. 2013;8:8–14.

    Google Scholar 

  68. Yamamoto T, Nakahigashi M, Umegae S, Kitagawa T, Matsumoto K. Impact of elemental diet on mucosal inflammation in patients with active Crohn’s disease: cytokine production and endoscopic and histological findings. Inflamm Bowel Dis. 2005;11:580–8.

    PubMed  Google Scholar 

  69. Sanchez-Muñoz F, Dominguez-Lopez A, Yamamoto-Furusho JK. Role of cytokines in inflammatory bowel disease. World J Gastroenterol. 2008;14:4280–8.

    PubMed  PubMed Central  Google Scholar 

  70. Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011;474:298–306.

    CAS  PubMed  Google Scholar 

  71. Maynard CL, Harrington LE, Janowski KM, Oliver JR, Zindl CL, Rudensky AY, et al. Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10. Nat Immunol. 2007;8:931–41.

    CAS  PubMed  Google Scholar 

  72. Shouval DS, Biswas A, Goettel JA, McCann K, Conaway E, Redhu NS, et al. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity. 2014;40:706–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Zigmond E, Bernshtein B, Friedlander G, Walker CR, Yona S, Kim KW, et al. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity. 2014;40:720–33.

    CAS  PubMed  Google Scholar 

  74. Eddie Ip WK, Hoshi N, Shouval DD, Snapper S, Medzhitov R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science (80-). 2017;356:513–9.

    Google Scholar 

  75. Mantovani A, Marchesi F. IL-10 and macrophages orchestrate gut homeostasis. Immunity. 2014;40:637–9. https://doi.org/10.1016/j.immuni.2014.04.015.

    Article  CAS  PubMed  Google Scholar 

  76. Keubler LM, Buettner M, Häger C, Bleich A. A multihit model: colitis lessons from the interleukin-10-deficient mouse. Inflamm Bowel Dis. 2015;21:1967–75.

    PubMed  Google Scholar 

  77. Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–74.

    PubMed  Google Scholar 

  78. Li B, Alli R, Vogel P, Geiger TL. IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis. Mucosal Immunol. 2014;7:869–78.

    CAS  PubMed  Google Scholar 

  79. Fedorak RN, Gangl A, Elson CO, Rutgeerts P, Schreiber S, Wild G, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. Gastroenterology. 2000;119:1473–82.

    CAS  PubMed  Google Scholar 

  80. Lindsay JO, Hodgson HJF. Review article: the immunoregulatory cytokine interleukin-10. A therapy for Crohn’s disease? Aliment Pharmacol Ther. 2001;15:1709–16.

    CAS  PubMed  Google Scholar 

  81. Schreiber S, Heinig T, Thiele HG, Raedler A. Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. Gastroenterology. 1995;108:1434–44.

    CAS  PubMed  Google Scholar 

  82. Marlow GJ, van Gent D, Ferguson LR. Why interleukin-10 supplementation does not work in Crohn’s disease patients. World J Gastroenterol. 2013;19:3931–41.

    PubMed  PubMed Central  Google Scholar 

  83. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677–86.

    CAS  PubMed  Google Scholar 

  84. Fleming BD, Chandrasekaran P, Dillon LAL, Dalby E, Suresh R, Sarkar A, et al. The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling. J Leukoc Biol. 2015;98:395–407.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Qualls JE, Kaplan AM, van Rooijen N, Cohen DA. Suppression of experimental colitis by intestinal mononuclear phagocytes. J Leukoc Biol. 2006;80:802–15.

    CAS  PubMed  Google Scholar 

  86. Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie ANJ, Van Rooijen N, et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007;178:4557–666.

    CAS  PubMed  Google Scholar 

  87. Chang H-H, Miaw S-C, Tseng W, Sun Y-W, Liu C-C, Tsao H-W, et al. PTPN22 modulates macrophage polarization and susceptibility to dextran sulfate sodium-induced colitis. J Immunol. 2013;191:2134–43. https://doi.org/10.4049/jimmunol.1203363.

    Article  CAS  PubMed  Google Scholar 

  88. Steinbach EC, Plevy SE. The role of macrophages and dendritic cells in the initiation of inflammation in IBD. Inflamm Bowel Dis. 2014;20:166–75.

    PubMed  Google Scholar 

  89. Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, et al. Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. J Clin Invest. 2008;118:2269–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreiber S, MacDermott RP, et al. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn’s disease. Clin Exp Immunol. 1993;94:174–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Rivollier A, He J, Kole A, Valatas V, Kelsall BL. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J Exp Med. 2012. https://doi.org/10.1084/jem.20101387.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Hunter MM, Wang A, Parhar KS, Johnston MJG, Van Rooijen N, Beck PL, et al. in vitro-derived alternatively activated macrophages reduce colonic inflammation in mice. Gastroenterology. 2010;138:1395–405. https://doi.org/10.1053/j.gastro.2009.12.041.

    Article  CAS  PubMed  Google Scholar 

  93. Leung G, Wang A, Fernando M, Phan VC, McKay DM. Bone marrow-derived alternatively activated macrophages reduce colitis without promoting fibrosis: participation of IL-10. Am J Physiol Gastrointest Liver Physiol. 2013;304:G781–G792792.

    CAS  PubMed  Google Scholar 

  94. Weisser SB, Brugger HK, Voglmaier NS, McLarren KW, van Rooijen N, Sly LM. SHIP-deficient, alternatively activated macrophages protect mice during DSS-induced colitis. J Leukoc Biol. 2011;90:483–92.

    CAS  PubMed  Google Scholar 

  95. Kühl AA, Erben U, Kredel LI, Siegmund B. Diversity of intestinal macrophages in inflammatory bowel diseases. Front Immunol. 2015;6:613.

    PubMed  PubMed Central  Google Scholar 

  96. Chandrasekaran P, Izadjoo S, Stimely J, Palaniyandi S, Zhu X, Tafuri W, et al. Regulatory macrophages inhibit alternative macrophage activation and attenuate pathology associated with fibrosis. J Immunol. 2019;203:2130–40.

    CAS  PubMed  Google Scholar 

  97. Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, et al. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab. 2007;6:446–57.

    PubMed  PubMed Central  Google Scholar 

  98. Franke TF, Yang S, Chan TO, Datta K, Kazlauskas A, Morrison DK, et al. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 1995;81:727–36.

    CAS  PubMed  Google Scholar 

  99. Arranz A, Doxaki C, Vergadi E, de la Martinez YT, Vaporidi K, Lagoudaki ED, et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci. 2012;109:517–22.

    Google Scholar 

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Funding

This research was funded by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Grant no. [RED-00570-16] and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Grant no. [Scholarship].

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  1. Laboratório de Biologia de Macrófagos e Monócitos, Departamento de Patologia Geral, Instituto de Ciências Biológicas-Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil

    Tamara Cristina Moreira Lopes & Ricardo Gonçalves

  2. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA

    David M. Mosser

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  1. Tamara Cristina Moreira Lopes
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TL and RG wrote the article and create the figures. DM wrote the article.

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Correspondence to Ricardo Gonçalves.

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Moreira Lopes, T.C., Mosser, D.M. & Gonçalves, R. Macrophage polarization in intestinal inflammation and gut homeostasis. Inflamm. Res. 69, 1163–1172 (2020). https://doi.org/10.1007/s00011-020-01398-y

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