Abstract
Autoimmune diseases (ADs) are featured by the body’s immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Currently, the exact pathogenesis of ADs remains not fully elucidated. Semaphorin-3A (Sema3A), a secreted member of semaphorin family, is a potent immunoregulator during all immune response stages. Sema3A has wide expression, such as in bone, connective tissue, kidney, neurons, and cartilage. Sema3A can downregulate ADs by suppressing the over-activity of both T-cell and B-cell autoimmunity. Moreover, Sema3A shows the ability to enhance T-cell and B-cell regulatory properties that control ADs, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis. However, it can also induce ADs when overexpressed. Together, these data strongly suggest that Sema3A plays a pivotal role in ADs, and it may be a promising treatment target for these diseases. In the present review, we focus on the immunological functions of Sema3A and summarize recent studies on the involvement of Sema3A in the pathogenesis of ADs; the discoveries obtained from recent findings may translate into novel therapeutic agent for ADs.
Similar content being viewed by others
Abbreviations
- ADs:
-
Autoimmune diseases
- αB-crystallin:
-
Alpha B-crystallin
- BAFF:
-
B-cell activating factor
- Bregs:
-
B regulatory cells
- CIA:
-
Collagen-induced arthritis
- CNS:
-
Central nervous system
- CpG-ODN:
-
Cytosine-phosphodiester-guanine oligodeoxynucleotides
- DAS28-CRP:
-
Disease Activity Score 28-joint count C reactive protein
- DCs:
-
Dendritic cells
- dSSc:
-
Diffuse systemic sclerosis
- EAE:
-
Experimental autoimmune encephalomyelitis
- FoxP3:
-
Forkhead box P3
- IL-2:
-
Interleukin 2
- IL-10:
-
Interleukin 10
- IL-17:
-
Interleukin 17
- IFNs:
-
Interferons
- ISSc:
-
Limited systemic sclerosis
- LGN:
-
Lupus glomerulonephritis
- MAG:
-
Myelin binding glycoprotein
- MAPK:
-
Ras/mitogen-activated protein kinase
- MOG:
-
Oligodendrocyte glycoprotein
- MS:
-
Multiple sclerosis
- NRP-1:
-
Neuropilin-1
- OA:
-
Osteoarthritis
- OPC:
-
Oligodendrocyte precursor cell
- PBMCs:
-
Peripheral blood mononuclear cells
- PSI:
-
Plexin–semaphorin–integrin
- RA:
-
Rheumatoid arthritis
- ROC:
-
Receiver operating characteristic
- RRMS:
-
Relapsing–remitting multiple sclerosis
- Sema3A:
-
Semaphorin-3A
- SLE:
-
Systemic lupus erythematosus
- SSc:
-
Systemic sclerosis
- TGF-β:
-
Transforming growth factor beta
- Th1:
-
Helper T-cell type 1
- Th17:
-
Helper T-cell type 17
- TNF:
-
Tumor necrosis factor
- Tregs:
-
Regulatory T cells
- VEGF:
-
Vascular endothelial growth factor
- VEGFR:
-
Vascular endothelial growth factor receptor
References
Ae K (1998) Angiogenesis: implication for rheumatoid arthritis. Arthritis Rheum 41:951–962
André S, Tough DF, Lacroix-Desmazes S, Kaveri SV, Bayry J (2009) Surveillance of antigen-presenting cells by CD4 + CD25 + regulatory T cells in autoimmunity. Am J Pathol 174:1575–1587. https://doi.org/10.2353/ajpath.2009.080987
Arizmendi-Vargas J, Carrillo-Ruiz JD, Lopez-Lizarraga ME, Martinez-Menchaca H, Serrato-Ávila JL, Rendón-Molina A, Rivera-Silva G (2011) Multiple sclerosis: an overview of the disease and current concepts of its pathophysiology. J Neurosci Behav Health 3:44–50
Bakke AC, Kirkland PA, Kitridou RC (1983) T lymphocyte subsets in systemic lupus erythematosus. Arthritis Rheum 26:745–750
Barresi V, Tuccari G (2010) Increased ratio of vascular endothelial growth factor to semaphorin3A is a negative prognostic factor in human meningiomas. Neuropathology 30:537–546. https://doi.org/10.1111/j.1440-1789.2010.01105.x
Brennan FM, McInnes IB (2008) Evidence that cytokines play a role in rheumatoid arthritis. J Clin Investig 118:3537–3545. https://doi.org/10.1172/jci36389
Bryan C, Howard Y, Brennan P, Black C, Silman A (1996) Survival following the onset of scleroderma: results from a retrospective inception cohort study of the UK patient population. J Rheumatol 35:1122–1126
Catalano A (2006) Semaphorin-3A is expressed by tumor cells and alters T-cell signal transduction and function. Blood 107:3321–3329. https://doi.org/10.1182/blood-2005-06-2445
Catalano A (2010) The neuroimmune semaphorin-3A reduces inflammation and progression of experimental autoimmune arthritis. J Immunol 185:6373–6383. https://doi.org/10.4049/jimmunol.0903527
Chang A, Tourtellotte WW, Rudick R, Trapp BD (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165–173. https://doi.org/10.1056/nejmoa010994
Clavel G et al (2007) Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very early arthritis and their association with inflammation and joint destruction. Clin Immunol 124:158–164
Committee SN (1999) Unified nomenclature for the semaphorin/collapsins. Cell 97:551–552
Costa C, Martínez-Sáez E, Gutiérrez-Franco A, Eixarch H, Castro Z, Ortega-Aznar A, Ramón y Cajal S, Montalban X, Espejo C (2015) Expression of semaphorin 3A, semaphorin 7A and their receptors in multiple sclerosis lesions. Mult Scler J 21:1632–1643. https://doi.org/10.1177/1352458515599848
Cozacov R, Halasz K, Haj T, Vadasz Z (2017) Semaphorin 3A: is a key player in the pathogenesis of asthma. Clin Immunol 184:70–72. https://doi.org/10.1016/j.clim.2017.05.011
Cvetanovich GL, Hafler DA (2010) Human regulatory T cells in autoimmune diseases. Curr Opin Immunol 22:753–760. https://doi.org/10.1016/j.coi.2010.08.012
de Larrinoa IRFF (2015) What is new in systemic lupus erythematosus. Reumatol Clin 11:27–32
De Winter F et al (2002) Injury-induced class 3 semaphorin expression in the rat spinal cord. Exp Neurol 175:61–75. https://doi.org/10.1006/exnr.2002.7884
Delaire S, Billard C, Tordjman R, Chédotal A, Elhabazi A, Bensussan A, Boumsell L (2001) Biological activity of soluble CD100. II. Soluble CD100, similarly to H-SemaIII, inhibits immune cell migration. J Immunol 166:4348–4354
Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15:545–558. https://doi.org/10.1038/nri3871
Distler O et al (2002) Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers. Arthritis Res 4:30
Distler O et al (2004) Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient skin angiogenesis in patients with systemic sclerosis. Circ Res 95:109–116
Eixarch H, Gutiérrez-Franco A, Montalban X, Espejo C (2013) Semaphorins 3A and 7A: potential immune and neuroregenerative targets in multiple sclerosis. Trends Mol Med 19:157–164. https://doi.org/10.1016/j.molmed.2013.01.003
Fiore R, Püschel AW (2003) The function of semaphorins during nervous system development. Front Biosci 8:s484–s499
Gagliardini V, Fankhauser C (1999) Semaphorin III can induce death in sensory neurons. Mol Cell Neurosci 14:301–316
Gao H et al (2017a) Expression and clinical significance of semaphorin 3A in serum and mononuclear cells in patients with systemic lupus erythematosus. Zhonghua Yi Xue Za Zhi 97:370–374. https://doi.org/10.3760/cma.j.issn.0376-2491.2017.05.010
Gao H, Ma XX, Guo Q, Zou YD, Zhong YC, Xie LF, Shao M, Zhang XW (2017b) Expression and clinical significance of semaphorin 3A in serum and monouclear cells in patients with systemic lupus erythematous. Natl Med J China 97:370–374
Guan SY, Leng RX, Khan MI, Qureshi H, Li XP, Ye DQ, Pan HF (2017) Interleukin-35: a potential therapeutic agent for autoimmune diseases. Inflammation 40:303–310. https://doi.org/10.1007/s10753-016-0453-9
Gutiérrez-Franco A et al (2016) Differential expression of sema3A and sema7A in a murine model of multiple sclerosis: implications for a therapeutic design. Clin Immunol 163:22–33. https://doi.org/10.1016/j.clim.2015.12.005
Huseby ES, Liggitt D, Brabb T, Schnabel B, Öhlén C, Goverman J (2001) A pathogenic role for myelin-specific Cd8 + T cells in a model for multiple sclerosis. J Exp Med 194:669–676. https://doi.org/10.1084/jem.194.5.669
Ji JD, Park-Min KH, Ivashkiv LB (2009) Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. Hum Immunol 70:211–217. https://doi.org/10.1016/j.humimm.2009.01.026
Kashiwagi H (2005) Negative regulation of platelet function by a secreted cell repulsive protein, semaphorin 3A. Blood 106:913–921. https://doi.org/10.1182/blood-2004-10-4092
Kawasaki T et al (2002) Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system. Development 129:671–680
Kim SJ (2015) Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases. Immunol Res 63:113–120. https://doi.org/10.1007/s12026-015-8694-5
Kolodkin AL, Matthes DJ, Goodman CS (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75:1389–1399. https://doi.org/10.1016/0092-8674(93)90625-Z
Kremer D, Hartung HP, Küry P (2015) Targeting semaphorins in MS as a treatment strategy to promote remyelination: a tale of mice, rats and men. Mult Scler J 21:1616–1617. https://doi.org/10.1177/1352458515608693
Kumanogoh A et al (2005) Semaphorins in the immune system. Int Congr Ser 1285:202–206. https://doi.org/10.1016/j.ics.2005.08.008
Kurosaka D et al (2010) Clinical significance of serum levels of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in patients with rheumatoid arthritis. J Rheumatol 37:1121–1128
Lepelletier Y et al (2006) Immunosuppressive role of semaphorin-3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization. Eur J Immunol 36:1782–1793. https://doi.org/10.1002/eji.200535601
Lerang K, Gilboe IM, Gran JT (2012) Differences between rheumatologists and other internists regarding diagnosis and treatment of systemic lupus erythematosus. Rheumatology (Oxford) 51:663–669. https://doi.org/10.1093/rheumatology/ker318
LeRoy E (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205
LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, Rowell N, Wollheim F (1998) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205
Li HM et al (2016) Emerging role of adipokines in systemic lupus erythematosus. Immunol Res 64:820–830. https://doi.org/10.1007/s12026-016-8808-8
Loes S, Kettunen P, Kvinnsland IH, Taniguchi M, Fujisawa H, Luukko K (2001) Expression of class 3 semaphorins and neuropilin receptors in the developing mouse tooth. Mech Dev 101:191–194. https://doi.org/10.1016/S0925-4773(00)00545-1
Lund FE, Randall TD (2010) Effector and regulatory B cells: modulators of CD4 + T cell immunity. Nat Rev Immunol 10:236. https://doi.org/10.1038/nri2729
Luo Y, Raible D, Raper JA (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75:217–227. https://doi.org/10.1016/0092-8674(93)80064-L
Mackiewicz Z, Sukura A, Povilenaite D, Ceponis A, Virtanen I, Hukkanen M, Konttinen YT (2002) Increased but imbalanced expression of VEGF and its receptors has no positive effect on angiogenesis in systemic sclerosis skin. Clin Exp Rheumatol 20:641–646
Majed HH et al (2006) A novel role for Sema3A in neuroprotection from injury mediated by activated microglia. J Neurosci 26:1730–1738. https://doi.org/10.1523/jneurosci.0702-05.2006
Messersmith EK, Leonardo ED, Shatz CJ, Tessier-Lavigne M, Goodman M, Kolodkin AL (1995) Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 14:949–959
Miao HQ, Soker S, Feiner L, Alonso JL, Raper JA, Klagsbrun M (1999) Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 146:233–242
Mizui M, Kumanogoh A, Kikutani H (2009) Immune semaphorins: novel features of neural guidance molecules. J Clin Immunol 29:1–11. https://doi.org/10.1007/s10875-008-9263-7
Mok CC, Lau CS (2003) Pathogenesis of systemic lupus erythematosus. J Clin Pathol 56:481–490
Moretti S, Procopio A, Lazzarini R, Rippo MR, Testa R, Marra M, Tamagnone L, Catalano A (2008) Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts. Blood 111:2290–2299. https://doi.org/10.1182/blood-2007-06096529
Navarra SV et al (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731. https://doi.org/10.1016/s0140-6736(10)61354-2
Negishi-Koga T, Takayanagi H (2012) Bone cell communication factors and semaphorins. Bonekey Rep 1:183
Okuno T, Nakatsuji Y, Kumanogoh A (2011) The role of immune semaphorins in multiple sclerosis. FEBS Lett 585:3829–3835. https://doi.org/10.1016/j.febslet.2011.03.033
Olewicz-Gawlik ASD, Samborski W (2016) Soluble semaphorin 3a and neuropilin-1: new markers for dysregulation of angiogenesis in systemic sclerosis. Ann Rheum Dis 75:749. https://doi.org/10.1136/annrheumdis-2016-eular.5233
Osada R, Horiuchi A, Kikuchi N, Ohira S, Ota M, Katsuyama Y, Konishi I (2006) Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas. Hum Pathol 37:1414–1425
Pan HF, Leng RX, Li XP, Zheng SG, Ye DQ (2013a) Targeting T-helper 9 cells and interleukin-9 in autoimmune diseases. Cytokine Growth Factor Rev 24:515–522
Pan HF, Li XP, Zheng SG, Ye DQ (2013b) Emerging role of interleukin-22 in autoimmune diseases. Cytokine Growth Factor Rev 24:51–57. https://doi.org/10.1016/j.cytogfr.2012.07.002
Perez SG et al (2016) Class 3 semaphorins modulate the invasive capacity of rheumatoid arthritis fibroblast-like synoviocytes. Anna Rheum Dis. https://doi.org/10.1136/annrheumdis-2016-209124.140
Piaton G et al (2011) Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system. Brain 134:1156–1167. https://doi.org/10.1093/brain/awr022
Püschel AW, Adams RH, Betz H (1995) Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension. Neuron 14:941–948
Ransohoff RM, Brown MA (2012) Innate immunity in the central nervous system. J Clin Investig 122:1164–1171. https://doi.org/10.1172/jci58644
Rezaeepoor M, Shapoori S, Ganjalikhani-hakemi M, Etemadifar M, Alsahebfosoul F, Eskandari N, Mansourian M (2017) Decreased expression of Sema3A, an immune modulator, in blood sample of multiple sclerosis patients. Gene 610:59–63. https://doi.org/10.1016/j.gene.2017.02.013
Rieger J, Wick W, Weller M (2003) Human malignant glioma cells express semaphorins and their receptors, neuropilins and plexins. Glia 42:379–389. https://doi.org/10.1002/glia.10210
Rimar D, Rosner I, Slobodin G, Boulman N, Rozenbaum M, Halasz K, Haj T, Jiries N, Kaly L, Vadasz Z (2014) Semaphorin 3a as a possible immunoregulator in systemic sclerosis. Ann Rheum Dis 73:868. https://doi.org/10.1136/annrheumdis-2014-eular.2948
Rimar D, Rosner I, Slobodin G, Rozenbaum M, Halasz K, Jiries N, Kaly L, Boulman N, Vadasz Z (2015a) Semaphorin 3A, a potential immune regulator in Familial Mediterranean fever. Pediatr Rheumatol 13:O46. https://doi.org/10.1186/1546-0096-13-s1-o46
Rimar D et al (2015b) Semaphorin 3A: an immunoregulator in systemic sclerosis. Rheumatol Int 35:1625–1630. https://doi.org/10.1007/s00296-015-3269-2
Romano E et al (2016) Decreased expression of neuropilin-1 as a novel key factor contributing to peripheral microvasculopathy and defective angiogenesis in systemic sclerosis. Ann Rheum Dis 75:1541–1549. https://doi.org/10.1136/annrheumdis-2015-207483
Roth L, Koncina E, Satkauskas S, Crémel G, Aunis D, Bagnard D (2008) The many faces of semaphorins: from development to pathology. Cell Mol Life Sci 66:649–666. https://doi.org/10.1007/s00018-008-8518-z
Rubio-Rivas M, Royo C, Simeón CP, Corbella X, Fonollosa V (2014) Mortality and survival in systemic sclerosis: systematic review and meta-analysis. Semin Arthritis Rheum 44:208–219. https://doi.org/10.1016/j.semarthrit.2014.05.010
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA (2010) Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 69:20–28. https://doi.org/10.1136/ard.2008.101766
Scarlato M (2003) Induction of neuropilins-1 and -2 and their ligands, Sema3A, Sema3F, and VEGF, during Wallerian degeneration in the peripheral nervous system. Exp Neurol 183:489–498. https://doi.org/10.1016/s0014-4886(03)00046-3
Schlahsa L, Zenk J, Aufderbeck S, Figueiredo C, Blasczyk R (2009) Soluble semaphorin 3A regulates the immune response. Hum Immunol 70:s157
Solomon BD, Mueller C, Chae WJ, Alabanza LM, Bynoe MS (2011) Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 108:2040–2045. https://doi.org/10.1073/pnas.1008721108
Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 66:940–944. https://doi.org/10.1136/ard.2006.066068
Suzuki K, Kumanogoh A, Kikutani H (2008) Semaphorins and their receptors in immune cell interactions. Nat Immunol 9:17–23. https://doi.org/10.1038/ni1553
Syed YA, Hand E, Mobius W, Zhao C, Hofer M, Nave KA, Kotter MR (2011) Inhibition of CNS remyelination by the presence of semaphorin 3A. J Neurosci 31:3719–3728. https://doi.org/10.1523/jneurosci.4930-10.2011
Takagawa S, Nakamura F, Kumagai K, Nagashima Y, Goshima Y, Saito T (2013a) Decreased Semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis. BMC Musculoskelet Disord 14:1–11
Takagawa S, Nakamura F, Kumagai K, Nagashima Y, Goshima Y, Saito T (2013b) Decreased semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis. BMC Musculoskelet Disord 14:40. https://doi.org/10.1186/1471-2474-14-40
Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM (1999) Plexin-neuropilin-1 complexes form functional semaphorin-3a receptors. Cell 99:59–69
Takamatsu H, Okuno T, Kumanogoh A (2010a) Regulation of immune cell responses by semaphorins and their receptors. Cell Mol Immunol 7:83–88. https://doi.org/10.1038/cmi.2009.111
Takamatsu H et al (2010b) Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat Immunol 11:594–600. https://doi.org/10.1038/ni.1885
Taniguchi M, Yuasa S, Fujisawa H, Naruse I, Saga S, Mishina M, Yagi T (1997) Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 19:519–530. https://doi.org/10.1016/S0896-6273(00)80368-2
Tran-Van H, Avota E, Bortlein C, Mueller N, Schneider-Schaulies S (2011) Measles virus modulates dendritic cell/T-cell communication at the level of plexinA1/neuropilin-1 recruitment and activity. Eur J Immunol 41:151–163. https://doi.org/10.1002/eji.201040847
Tubridy N et al (1999) The effect of anti-α4 integrin antibody on brain lesion activity in MS. Neurology 53:466. https://doi.org/10.1212/wnl.53.3.466
Vadasz Z, Toubi E (2012) Semaphorin 3A: a marker for disease activity and a potential putative disease-modifying treatment in systemic lupus erythematosus. Lupus 21:1266–1270. https://doi.org/10.1177/0961203312456753
Vadasz Z, Toubi E (2013) Semaphorins: their dual role in regulating immune-mediated diseases. Clinic Rev Allerg Immunol 47:17–25. https://doi.org/10.1007/s12016-013-8360-4
Vadasz Z, Attias D, Kessel A, Toubi E (2010) Neuropilins and semaphorins: from angiogenesis to autoimmunity. Autoimmun Rev 9:825–829. https://doi.org/10.1016/j.autrev.2010.07.014
Vadasz Z, Ben-Izhak O, Bejar J, Sabo E, Kessel A, Storch S, Toubi E (2011) The involvement of immune semaphorins and neuropilin-1 in lupus nephritis. Lupus 20:1466–1473. https://doi.org/10.1177/0961203311417034
Vadasz Z et al (2012a) Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus. Arthritis Res Ther 14:R146. https://doi.org/10.1186/ar3881
Vadasz Z, Haj T, Halasz K, Rosner I, Slobodin G, Attias D, Kessel A, Kessler O, Neufeld G, Toubi E (2012b) Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus. Arthritis Res Ther 14:1–8
Vadasz Z et al (2014) A regulatory role for CD72 expression on B cells in systemic lupus erythematosus. Semin Arthritis Rheum 43:767–771. https://doi.org/10.1016/j.semarthrit.2013.11.010
Vadasz Z, Peri R, Eiza N, Slobodin G, Balbir-Gurman A, Toubi E (2015a) The expansion of CD25 high IL-10 high FoxP3 high B regulatory cells is in association with SLE disease activity. J Immunol Res 2015:254245. https://doi.org/10.1155/2015/254245
Vadasz Z, Rainis T, Nakhleh A, Haj T, Bejar J, Halasz K, Toubi E (2015b) The involvement of immune semaphorins in the pathogenesis of inflammatory bowel diseases (IBDs). PLoS ONE 10:e0125860. https://doi.org/10.1371/journal.pone.0125860
Vadasz Z, Rimar D, Toubi E (2015c) A6.14 Semaphorin 3A, an immunoregulator and potential biomarker for disease severity in systemic sclerosis. Ann Rheum Dis 74:A61. https://doi.org/10.1136/annrheumdis-2015-207259.140
Villegas G, Tufro A (2002) Ontogeny of semaphorins 3A and 3F and their receptors neuropilins 1 and 2 in the kidney. Mech Dev 199:S149–S153
Williams A et al (2007) Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain 130:2554–2565. https://doi.org/10.1093/brain/awm202
Wright DE, White FR, Gerfen RW, Silos-Santiago I, Snider W (1995) The guidance molecule semaphorin III is expressed in regions of spinal cord and periphery avoided by growing sensory axons. J Comp Neurol 361:321–333
Yamamoto M et al (2008) Plexin-A4 negatively regulates T lymphocyte responses. Int Immunol 20:413–420. https://doi.org/10.1093/intimm/dxn006
Yazdani U, Terman JR (2006) The semaphorins. Genome Biol 7:211. https://doi.org/10.1186/gb-2006-7-3-211
Yoshida Y et al (2014) AB0114 Semaphorin3A and semaphorin4d in rheumatoid arthritis. Ann Rheum Dis 72:A820. https://doi.org/10.1136/annrheumdis-2013-eular.2437
Yu C, Gershwin ME, Chang C (2014) Diagnostic criteria for systemic lupus erythematosus: a critical review. J Autoimmun 49:10–13
Yuan X, Cheng G, Malek TR (2014) The importance of regulatory T-cell heterogeneity in maintaining self-tolerance. Immunol Rev 259:103–114. https://doi.org/10.1111/imr.12163
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (81573222). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Liu, LN., Li, XM., Ye, DQ. et al. Emerging role of semaphorin-3A in autoimmune diseases. Inflammopharmacol 26, 655–665 (2018). https://doi.org/10.1007/s10787-018-0484-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-018-0484-y