title: Semaphorins: their dual role in regulating immune-mediated diseases.
abstract: The semaphorin family members were originally considered to play a role in neurodevelopment, angiogenesis, tumor development, and metastasis. Over the past few years, a growing body of data indicates that semaphorins are involved in the regulation of the immune system, identified in this case as the "immune semaphorins." These semaphorins are involved in almost all phases of both normal and pathological immune responses and were demonstrated to participate in allergic diseases as well as in auto-immune pathologies. Some of them, such as semaphorin 3A (sema3A), is important in downregulating autoimmune diseases by suppressing the over-activity of both T and B cell autoimmunity. In addition, sema3A was shown to enhance the ability of T and B cell regulatory properties and by doing so to control autoimmune diseases, such as systemic lupus erythematosus. Other semaphorins, such as semaphorins 4D and 4A are important in stimulating T and B cells, thus keeping these immune responses on-going. However, when overexpressed, they can induce the induction of many immune-mediated diseases. The importance of all this is to develop targeting therapies that could possibly enhance or alternatively suppress these molecules. In this review, we will focus on several immune semaphorins--their role in immune homeostasis and in immune-mediated diseases.
authors: Bnai Zion Medical Center, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: Zahava
authors: Z
authors: Vadasz
authors: Elias
authors: E
authors: Toubi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy; D039961:Semaphorins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D039961:Semaphorins
references: Immunity. 1999 Oct;11(4):495-506
references: 10549631
references: Nature. 2007 Apr 5;446(7136):680-4
references: 17377534
references: Arthritis Rheum. 2011 Aug;63(8):2484-94
references: 21484765
references: J Leukoc Biol. 2012 Jan;91(1):7-13
references: 21878545
references: Blood. 2006 Apr 15;107(8):3321-9
references: 16380453
references: Stem Cells Dev. 2010 Jul;19(7):1075-9
references: 19886821
references: Trends Cell Biol. 2000 Sep;10(9):377-83
references: 10932095
references: J Dermatol Sci. 2012 Apr;66(1):37-43
references: 22381253
references: Immunity. 2000 Nov;13(5):633-42
references: 11114376
references: Ann N Y Acad Sci. 2009 Feb;1153:20-8
references: 19236324
references: Immunology. 2009 Sep;128(1):114-22
references: 19689741
references: FEBS Lett. 2011 Dec 1;585(23):3829-35
references: 21420960
references: Cell Mol Life Sci. 2005 Jun;62(12):1363-71
references: 15818466
references: J Exp Med. 2005 Aug 1;202(3):437-44
references: 16043519
references: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13015-20
references: 18728195
references: Immunity. 2000 Nov;13(5):621-31
references: 11114375
references: J Clin Immunol. 2009 Jan;29(1):1-11
references: 19067132
references: Tissue Antigens. 2000 May;55(5):429-36
references: 10885563
references: J Immunol. 2002 Aug 1;169(3):1175-81
references: 12133937
references: Mucosal Immunol. 2012 Jul;5(4):409-19
references: 22472774
references: Nat Rev Immunol. 2003 Feb;3(2):159-67
references: 12563299
references: J Immunol. 2004 Jan 15;172(2):1246-55
references: 14707103
references: J Immunol. 2006 Sep 1;177(5):3406-12
references: 16920982
references: Nat Rev Immunol. 2008 Aug;8(8):577-80
references: 18617884
references: Scand J Immunol. 2002 Sep;56(3):270-5
references: 12193228
references: J Exp Med. 2007 May 14;204(5):1083-93
references: 17485510
references: Crit Rev Immunol. 2003;23(1-2):65-81
references: 12906260
references: Blood. 1990 Apr 1;75(7):1404-7
references: 2317557
references: Blood. 2001 Jun 1;97(11):3498-504
references: 11369643
references: Dev Dyn. 2008 Jun;237(6):1699-708
references: 18489001
references: Trends Mol Med. 2005 Aug;11(8):362-9
references: 16002337
references: J Clin Immunol. 2009 Jan;29(1):12-21
references: 19067131
references: J Immunol. 2006 Oct 1;177(7):4311-21
references: 16982865
references: Eur J Immunol. 2006 Jul;36(7):1782-93
references: 16791896
references: Genome Biol. 2006;7(3):211
references: 16584533
references: Int Immunol. 2005 Oct;17(10):1277-82
references: 16113236
references: Int Immunol. 2003 Aug;15(8):1027-34
references: 12882840
references: J Immunol. 2010 Nov 15;185(10):6373-83
references: 20937848
references: Hum Immunol. 2009 Apr;70(4):211-7
references: 19480842
references: J Pharmacol Sci. 2011;117(1):34-44
references: 21852750
references: Curr Opin Struct Biol. 2004 Dec;14(6):669-78
references: 15582390
references: Arthritis Res Ther. 2012 Jun 14;14(3):R146
references: 22697500
references: Am J Pathol. 1998 Jul;153(1):255-62
references: 9665486
references: J Dermatol Sci. 2011 Jun;62(3):176-82
references: 21524887
references: Blood. 2008 Feb 15;111(4):2290-9
references: 18056484
references: J Cell Sci. 2003 Sep 1;116(Pt 17):3463-70
references: 12893810
references: Immunity. 2005 Mar;22(3):305-16
references: 15780988
references: J Immunol. 2001 Oct 15;167(8):4321-8
references: 11591755
references: Nature. 2002 Oct 10;419(6907):629-33
references: 12374982
references: Int Immunol. 2008 Mar;20(3):413-20
references: 18209113
references: Acta Derm Venereol. 2012 Sep;92(5):521-8
references: 22565412
references: J Immunol. 2010 Feb 1;184(3):1499-506
references: 20038643
references: J Clin Immunol. 2011 Feb;31(1):30-8
references: 20922561
references: Eur J Immunol. 2002 Feb;32(2):561-7
references: 11828373
references: J Invest Dermatol. 2008 Jan;128(1):151-61
references: 17671519
references: BMC Immunol. 2011 May 19;12:30
references: 21595947
references: Immunol Res. 2011 May;50(1):10-21
references: 21203905
references: Nat Immunol. 2008 Jan;9(1):17-23
references: 18087252
references: Trends Immunol. 2012 Mar;33(3):127-35
references: 22325954
references: Autoimmunity. 2011 Aug;44(5):427-36
references: 21244334
references: Curr Med Chem. 2010;17(30):3462-75
references: 20738252
references: Immunol Res. 2008;41(3):217-22
references: 18649144