title: Pivotal roles of GM-CSF in autoimmunity and inflammation.
abstract: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4(+) T cells. Therefore, the mechanism of GM-CSF-producing CD4(+) T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Shiomi
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Usui
mesh_terms: D000818:Animals; D015551:Autoimmunity; D003424:Crohn Disease / Q000209:etiology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology; D011649:Pulmonary Alveolar Proteinosis / Q000209:etiology / Q000276:immunology
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
references.citation: J Immunol. 2006 Jul 1;177(1):566-73
references.pmid: 16785554
references.citation: Sci Transl Med. 2014 Jun 18;6(241):241ra80
references.pmid: 24944195
references.citation: Exp Cell Res. 1993 Jun;206(2):311-7
references.pmid: 7684696
references.citation: J Exp Med. 2008 Sep 29;205(10):2281-94
references.pmid: 18779348
references.citation: J Immunol. 2002 Sep 1;169(5):2498-506
references.pmid: 12193719
references.citation: Cell Res. 2008 Dec;18(12):1220-9
references.pmid: 19030026
references.citation: J Exp Med. 2007 Aug 6;204(8):1849-61
references.pmid: 17635957
references.citation: Trends Immunol. 2002 Aug;23(8):403-8
references.pmid: 12133803
references.citation: Semin Immunol. 2013 Nov 15;25(4):305-12
references.pmid: 24211039
references.citation: J Immunol. 2012 Apr 1;188(7):3107-15
references.pmid: 22345669
references.citation: Ann Rheum Dis. 2011 Sep;70(9):1542-9
references.pmid: 21613310
references.citation: Am Rev Respir Dis. 1987 Oct;136(4):811-7
references.pmid: 2821854
references.citation: Nat Immunol. 2007 Jun;8(6):639-46
references.pmid: 17486092
references.citation: N Engl J Med. 2009 Dec 31;361(27):2679-81
references.pmid: 20042763
references.citation: Am J Respir Crit Care Med. 2010 Jun 15;181(12):1345-54
references.pmid: 20167854
references.citation: Am J Respir Crit Care Med. 2006 Feb 1;173(3):310-7
references.pmid: 16239626
references.citation: Arthritis Res. 2001;3(5):293-8
references.pmid: 11549370
references.citation: Eur Respir J. 2011 Dec;38(6):1361-7
references.pmid: 21478218
references.citation: N Engl J Med. 2001 Aug 16;345(7):517-25
references.pmid: 11519507
references.citation: Arthritis Rheum. 2009 May;60(5):1352-61
references.pmid: 19404955
references.citation: Respir Res. 2012;13:46
references.pmid: 22697800
references.citation: Nat Immunol. 2011 Mar;12(3):231-8
references.pmid: 21240265
references.citation: Arthritis Rheum. 1996 Jan;39(1):115-24
references.pmid: 8546720
references.citation: N Engl J Med. 2007 Feb 8;356(6):567-79
references.pmid: 17287477
references.citation: J Pharmacol Exp Ther. 1992 Feb;260(2):680-8
references.pmid: 1371158
references.citation: J Immunol. 1989 Feb 1;142(3):813-8
references.pmid: 2521509
references.citation: J Immunol. 2004 Oct 1;173(7):4643-51
references.pmid: 15383599
references.citation: J Exp Med. 1996 Aug 1;184(2):695-706
references.pmid: 8760823
references.citation: Inflamm Bowel Dis. 2012 Jul;18(7):1333-9
references.pmid: 22552871
references.citation: J Allergy Clin Immunol. 2003 Oct;112(4):653-65; quiz 666
references.pmid: 14564341
references.citation: Cytokine. 1996 Jun;8(6):501-6
references.pmid: 8818548
references.citation: Thorax. 2009 Dec;64(12):1044-52
references.pmid: 19850966
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L715-31
references.pmid: 20363851
references.citation: Nature. 2010 Oct 21;467(7318):967-71
references.pmid: 20962846
references.citation: Curr Opin Immunol. 2011 Dec;23(6):702-6
references.pmid: 21899997
references.citation: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5592-6
references.pmid: 8202532
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4560-5
references.pmid: 15070757
references.citation: J Allergy Clin Immunol. 2000 Jun;105(6 Pt 1):1146-52
references.pmid: 10856149
references.citation: Eur J Immunol. 2011 Sep;41(9):2585-95
references.pmid: 21660938
references.citation: Ann Surg. 1994 Jul;220(1):68-76
references.pmid: 8024361
references.citation: Am J Respir Crit Care Med. 2002 Jul 15;166(2):215-35
references.pmid: 12119235
references.citation: Brain Res. 2012 May 9;1453:77-86
references.pmid: 22483960
references.citation: Rheumatology (Oxford). 2008 Jun;47(6):753-9
references.pmid: 18356170
references.citation: J Leukoc Biol. 1996 Apr;59(4):481-8
references.pmid: 8613693
references.citation: Gastroenterology. 2009 Apr;136(4):1261-71, e1-3
references.pmid: 19230854
references.citation: Am J Physiol Gastrointest Liver Physiol. 2014 Mar;306(6):G455-65
references.pmid: 24503766
references.citation: J Neuroimmunol. 2014 Sep 15;274(1-2):1-13
references.pmid: 25091432
references.citation: J Exp Med. 1989 Aug 1;170(2):577-82
references.pmid: 2666563
references.citation: J Immunol. 2001 Feb 1;166(3):2090-9
references.pmid: 11160260
references.citation: Blood. 2009 Apr 2;113(14):3190-7
references.pmid: 19196868
references.citation: Nat Immunol. 2011 Mar;12(3):255-63
references.pmid: 21278737
references.citation: J Immunol. 2014 Jul 15;193(2):849-59
references.pmid: 24951817
references.citation: Mol Biol Cell. 1994 Jan;5(1):119-28
references.pmid: 8186461
references.citation: Chest. 2006 Jul;130(1):227-37
references.pmid: 16840407
references.citation: Clin Exp Immunol. 1997 Jul;109(1):4-11
references.pmid: 9218817
references.citation: J Immunol. 2007 Jul 15;179(2):1198-209
references.pmid: 17617613
references.citation: EMBO J. 1989 Feb;8(2):441-8
references.pmid: 2542015
references.citation: J Exp Med. 2014 Jun 2;211(6):1243-56
references.pmid: 24821911
references.citation: Blood. 2008 Jan 15;111(2):485-91
references.pmid: 18182579
references.citation: N Engl J Med. 2003 Dec 25;349(26):2527-39
references.pmid: 14695413
references.citation: J Exp Med. 2012 Jul 30;209(8):1505-17
references.pmid: 22802353
references.citation: Ann Rheum Dis. 1997 Jun;56(6):364-8
references.pmid: 9227165
references.citation: Gut. 2007 Jan;56(1):2-5
references.pmid: 17172582
references.citation: Immunol Cell Biol. 2001 Aug;79(4):376-84
references.pmid: 11488985
references.citation: Blood. 1989 Dec;74(8):2769-70
references.pmid: 2510837
references.citation: Immunopharmacol Immunotoxicol. 1998 Aug;20(3):373-82
references.pmid: 9736442
references.citation: Mol Cell Biol. 2004 Sep;24(18):7914-30
references.pmid: 15340054
references.citation: Cell Immunol. 2002 Oct;219(2):92-7
references.pmid: 12576027
references.citation: Inflamm Bowel Dis. 2008 Jan;14(1):88-99
references.pmid: 17932977
references.citation: Eur Respir J. 2000 Nov;16(5):959-64
references.pmid: 11153599
references.citation: J Clin Invest. 1996 Feb 15;97(4):1102-10
references.pmid: 8613534
references.citation: Nat Rev Rheumatol. 2009 Oct;5(10):554-9
references.pmid: 19798030
references.citation: Clin Immunol. 2010 May;135(2):223-35
references.pmid: 20338813
references.citation: EMBO J. 2006 Feb 8;25(3):479-89
references.pmid: 16437163
references.citation: Am J Hum Genet. 2001 Mar;68(3):674-85
references.pmid: 11179015
references.citation: Blood. 2004 Feb 1;103(3):820-7
references.pmid: 12920017
references.citation: Z Rheumatol. 1992 May-Jun;51(3):121-6
references.pmid: 1502858
references.citation: Lancet. 2011 Dec 3;378(9807):1949-61
references.pmid: 21719092
references.citation: J Immunol. 2000 Jul 1;165(1):49-58
references.pmid: 10861034
references.citation: Cytokine Growth Factor Rev. 2013 Jun;24(3):189-201
references.pmid: 23535386
references.citation: Am J Respir Cell Mol Biol. 2007 Jan;36(1):114-21
references.pmid: 16917076
references.citation: Nature. 2003 Nov 27;426(6965):454-60
references.pmid: 14647385
references.citation: Pharmacol Ther. 2006 Oct;112(1):106-15
references.pmid: 16716406
references.citation: J Clin Invest. 2009 Jan;119(1):61-9
references.pmid: 19075395
references.citation: Trends Immunol. 2013 Feb;34(2):81-9
references.pmid: 23000011
references.citation: Int Arch Allergy Immunol. 1998 Dec;117(4):248-54
references.pmid: 9876226
references.citation: Arthritis Rheumatol. 2014 Jul;66(7):1955-60
references.pmid: 24692225
references.citation: J Biol Chem. 1977 Mar 25;252(6):1998-2003
references.pmid: 300377
references.citation: J Exp Med. 2001 Oct 1;194(7):873-82
references.pmid: 11581310
references.citation: Cell Res. 2014 Dec;24(12):1387-402
references.pmid: 25412660
references.citation: J Exp Med. 2008 Aug 4;205(8):1903-16
references.pmid: 18663128
references.citation: J Exp Med. 1989 Sep 1;170(3):865-75
references.pmid: 2504878
references.citation: Expert Rev Gastroenterol Hepatol. 2010 Dec;4(6):723-31
references.pmid: 21108592
references.citation: Chest. 2013 Mar;143(3):814-24
references.pmid: 23460159
references.citation: Arthritis Rheum. 2011 Aug;63(8):2504-15
references.pmid: 21381000
references.citation: J Immunol. 1998 Oct 1;161(7):3639-44
references.pmid: 9759887
references.citation: Chron Respir Dis. 2011;8(1):53-82
references.pmid: 21339375
references.citation: Ann Rheum Dis. 2013 Sep 1;72(9):1445-52
references.pmid: 23234647
references.citation: J Immunol. 2003 Dec 1;171(11):6173-7
references.pmid: 14634133
references.citation: Nat Immunol. 2011 Jun;12(6):568-75
references.pmid: 21516111
references.citation: J Immunol. 2000 Mar 1;164(5):2602-9
references.pmid: 10679099
references.citation: Nat Immunol. 2011 Jun;12(6):560-7
references.pmid: 21516112
references.citation: J Neuroinflammation. 2014;11:201
references.pmid: 25441979
references.citation: Eur J Immunol. 2007 Sep;37(9):2518-28
references.pmid: 17694571
references.citation: Semin Immunol. 2012 Jun;24(3):225-30
references.pmid: 22425228
references.citation: Annu Rev Physiol. 2002;64:775-802
references.pmid: 11826288
references.citation: J Neuroimmunol. 1993 Jun;45(1-2):193-201
references.pmid: 8331161
references.citation: Mol Immunol. 2012 Aug;52(1):30-7
references.pmid: 22580403
references.citation: Blood. 1990 Nov 15;76(10):1989-96
references.pmid: 1700731
references.citation: Science. 1994 Apr 29;264(5159):713-6
references.pmid: 8171324
references.citation: Nat Immunol. 2011 Jun;12(6):521-2
references.pmid: 21587311
references.citation: J Neuroinflammation. 2012;9:268
references.pmid: 23234315
references.citation: Cell Host Microbe. 2010 Feb 18;7(2):151-63
references.pmid: 20159620
references.citation: Immunol Rev. 2006 Oct;213:48-65
references.pmid: 16972896
references.citation: Lancet. 2002 Nov 9;360(9344):1478-80
references.pmid: 12433518
references.citation: Eur Neurol. 1993;33(2):152-5
references.pmid: 8467823
references.citation: J Immunol. 1987 Aug 15;139(4):1113-9
references.pmid: 3038997
references.citation: World J Gastroenterol. 2006 Nov 14;12(42):6751-5
references.pmid: 17106921
references.citation: J Pathol. 2003 Nov;201(3):343-54
references.pmid: 14595745
references.citation: J Immunol. 1986 Apr 1;136(7):2348-57
references.pmid: 2419430
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: Nat Rev Immunol. 2008 Jul;8(7):533-44
references.pmid: 18551128
references.citation: Inflamm Bowel Dis. 2010 Mar;16(3):428-41
references.pmid: 19639560
references.citation: J Immunol. 1995 Jun 1;154(11):5842-50
references.pmid: 7538533
references.citation: J Immunol. 2012 Jul 15;189(2):906-15
references.pmid: 22696442
references.citation: Immunity. 2001 Oct;15(4):557-67
references.pmid: 11672538
references.citation: Eur J Immunol. 1992 Jun;22(6):1447-54
references.pmid: 1601035
references.citation: Blood. 1999 Jan 15;93(2):655-66
references.pmid: 9885228
references.citation: Ther Adv Musculoskelet Dis. 2013 Jun;5(3):141-52
references.pmid: 23858337
references.citation: J Exp Med. 2010 Jun 7;207(6):1135-43
references.pmid: 20457757
references.citation: J Neuroinflammation. 2012;9:82
references.pmid: 22540228
references.citation: J Clin Invest. 1999 Feb;103(4):563-9
references.pmid: 10021465
references.citation: J Immunol. 2007 Apr 15;178(8):5245-52
references.pmid: 17404308
references.citation: J Immunol. 2003 Dec 15;171(12):6846-55
references.pmid: 14662891
references.citation: PLoS One. 2012;7(7):e40523
references.pmid: 22808181
references.citation: Drug Res (Stuttg). 2013 Nov;63 Suppl 1:S8
references.pmid: 24242041
references.citation: Blood. 1997 Oct 15;90(8):3037-49
references.pmid: 9376584
references.citation: J Immunol. 2014 Sep 1;193(5):2438-54
references.pmid: 25049355
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11354-9
references.pmid: 9736740
references.citation: Eur J Immunol. 1996 Mar;26(3):648-52
references.pmid: 8605933
references.citation: Ann Rheum Dis. 2015 Jun;74(6):1058-64
references.pmid: 24534756
references.citation: Immunopharmacol Immunotoxicol. 2006;28(2):295-304
references.pmid: 16873097
references.citation: N Engl J Med. 2005 May 26;352(21):2193-201
references.pmid: 15917384
references.citation: Shock. 2008 Oct;30(4):434-42
references.pmid: 18277945
references.citation: Biochem Biophys Res Commun. 2003 Dec 26;312(4):897-902
references.pmid: 14651956
references.citation: Exp Lung Res. 2012 Mar;38(2):55-66
references.pmid: 22185348
references.citation: Blood. 2002 Dec 1;100(12):4193-200
references.pmid: 12393686
references.citation: Immunity. 2012 Jun 29;36(6):1031-46
references.pmid: 22749353
references.citation: Crit Rev Immunol. 2005;25(5):405-28
references.pmid: 16167889
references.citation: Am Rev Respir Dis. 1986 Mar;133(3):450-4
references.pmid: 3485395
references.citation: Semin Arthritis Rheum. 2013 Oct;43(2):158-70
references.pmid: 24157091
references.citation: Nature. 2012 Apr 26;484(7395):514-8
references.pmid: 22466287
references.citation: Science. 2012 Feb 3;335(6068):597-601
references.pmid: 22245738
references.citation: J Immunol. 2002 Dec 1;169(11):6332-42
references.pmid: 12444140
references.citation: Nature. 2011 Jun 16;474(7351):307-17
references.pmid: 21677747
references.citation: Am J Respir Crit Care Med. 1994 Oct;150(4):1038-48
references.pmid: 7921434
references.citation: J Clin Invest. 1989 Mar;83(3):876-82
references.pmid: 2646320
references.citation: J Immunol. 2014 Jul 1;193(1):120-9
references.pmid: 24890729
references.citation: J Immunol. 2011 May 1;186(9):5468-77
references.pmid: 21421852
references.citation: Eur Respir J. 2009 May;33(5):1220-2
references.pmid: 19407056
references.citation: Int Immunol. 1999 Dec;11(12):1945-56
references.pmid: 10590260
references.citation: Eur J Immunol. 2010 Aug;40(8):2174-81
references.pmid: 20486123
references.citation: Cell. 2008 Aug 8;134(3):496-507
references.pmid: 18692472
references.citation: J Exp Med. 2010 May 10;207(5):953-61
references.pmid: 20421390
references.citation: Cell Immunol. 2005 Oct;237(2):123-30
references.pmid: 16386239
references.citation: Cell Signal. 2014 Feb;26(2):192-7
references.pmid: 24219909
references.citation: Gut. 2009 Oct;58(10):1354-62
references.pmid: 19505878
references.citation: J Immunol. 2007 Jan 1;178(1):39-48
references.pmid: 17182538
references.citation: J Immunol. 2004 Nov 15;173(10):6384-92
references.pmid: 15528378
references.citation: J Immunol. 1991 Aug 15;147(4):1238-46
references.pmid: 1714478
references.citation: Ann Neurol. 2009 Sep;66(3):390-402
references.pmid: 19810097
references.citation: Neurobiol Dis. 2006 Oct;24(1):183-93
references.pmid: 16901708