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Inflammopharmacology

, Volume 26, Issue 3, pp 655–665 | Cite as

Emerging role of semaphorin-3A in autoimmune diseases

  • Li-Na Liu
  • Xiao-Mei Li
  • Dong-Qing Ye
  • Hai-Feng Pan
Review

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.

Keywords

Semaphorin-3A Therapeutic agent Autoimmune diseases 

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

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Ae K (1998) Angiogenesis: implication for rheumatoid arthritis. Arthritis Rheum 41:951–962CrossRefGoogle Scholar
  2. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  3. 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 3:44–50Google Scholar
  4. Bakke AC, Kirkland PA, Kitridou RC (1983) T lymphocyte subsets in systemic lupus erythematosus. Arthritis Rheum 26:745–750PubMedCrossRefGoogle Scholar
  5. 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 PubMedCrossRefGoogle Scholar
  6. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  7. 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 35:1122–1126CrossRefGoogle Scholar
  8. 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 PubMedCrossRefGoogle Scholar
  9. 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 PubMedCrossRefGoogle Scholar
  10. 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 PubMedCrossRefGoogle Scholar
  11. 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 124:158–164PubMedCrossRefGoogle Scholar
  12. Committee SN (1999) Unified nomenclature for the semaphorin/collapsins. Cell 97:551–552CrossRefGoogle Scholar
  13. 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 CrossRefGoogle Scholar
  14. 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 PubMedCrossRefGoogle Scholar
  15. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  16. de Larrinoa IRFF (2015) What is new in systemic lupus erythematosus. Reumatol Clin 11:27–32CrossRefGoogle Scholar
  17. 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 PubMedCrossRefGoogle Scholar
  18. 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 166:4348–4354PubMedCrossRefGoogle Scholar
  19. Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15:545–558.  https://doi.org/10.1038/nri3871 PubMedCrossRefGoogle Scholar
  20. 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 4:30CrossRefGoogle Scholar
  21. 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 95:109–116PubMedCrossRefGoogle Scholar
  22. 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 PubMedCrossRefGoogle Scholar
  23. Fiore R, Püschel AW (2003) The function of semaphorins during nervous system development. Front Biosci 8:s484–s499PubMedCrossRefGoogle Scholar
  24. Gagliardini V, Fankhauser C (1999) Semaphorin III can induce death in sensory neurons. Mol Cell Neurosci 14:301–316PubMedCrossRefGoogle Scholar
  25. 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 PubMedCrossRefGoogle Scholar
  26. 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 97:370–374Google Scholar
  27. 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 PubMedCrossRefGoogle Scholar
  28. 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 PubMedCrossRefGoogle Scholar
  29. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  30. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  31. 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 PubMedCrossRefGoogle Scholar
  32. Kawasaki T et al (2002) Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system. Development 129:671–680PubMedGoogle Scholar
  33. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  34. 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 PubMedCrossRefGoogle Scholar
  35. 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 CrossRefGoogle Scholar
  36. 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 CrossRefGoogle Scholar
  37. 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 37:1121–1128PubMedCrossRefGoogle Scholar
  38. 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 PubMedCrossRefGoogle Scholar
  39. 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 CrossRefGoogle Scholar
  40. LeRoy E (1988) Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 15:202–205PubMedGoogle Scholar
  41. 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 15:202–205Google Scholar
  42. 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 PubMedCrossRefGoogle Scholar
  43. 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 PubMedCrossRefGoogle Scholar
  44. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  45. 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 PubMedCrossRefGoogle Scholar
  46. 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 20:641–646PubMedGoogle Scholar
  47. 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 PubMedCrossRefGoogle Scholar
  48. 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 14:949–959PubMedCrossRefGoogle Scholar
  49. 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 146:233–242PubMedPubMedCentralGoogle Scholar
  50. 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 PubMedCrossRefGoogle Scholar
  51. Mok CC, Lau CS (2003) Pathogenesis of systemic lupus erythematosus. J Clin Pathol 56:481–490PubMedPubMedCentralCrossRefGoogle Scholar
  52. 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 PubMedCrossRefGoogle Scholar
  53. 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 PubMedCrossRefGoogle Scholar
  54. Negishi-Koga T, Takayanagi H (2012) Bone cell communication factors and semaphorins. Bonekey Rep 1:183PubMedPubMedCentralCrossRefGoogle Scholar
  55. 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 PubMedCrossRefGoogle Scholar
  56. 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 CrossRefGoogle Scholar
  57. 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 37:1414–1425PubMedCrossRefGoogle Scholar
  58. 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 24:515–522PubMedCrossRefGoogle Scholar
  59. 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 PubMedCrossRefGoogle Scholar
  60. 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 CrossRefGoogle Scholar
  61. 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 PubMedCrossRefGoogle Scholar
  62. 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 14:941–948PubMedCrossRefGoogle Scholar
  63. Ransohoff RM, Brown MA (2012) Innate immunity in the central nervous system. J Clin Investig 122:1164–1171.  https://doi.org/10.1172/jci58644 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 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 PubMedCrossRefGoogle Scholar
  65. 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 PubMedCrossRefGoogle Scholar
  66. 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 CrossRefGoogle Scholar
  67. 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 CrossRefGoogle Scholar
  68. 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 PubMedCrossRefGoogle Scholar
  69. 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 PubMedCrossRefGoogle Scholar
  70. 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 CrossRefGoogle Scholar
  71. 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 PubMedCrossRefGoogle Scholar
  72. 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 PubMedCrossRefGoogle Scholar
  73. 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 PubMedCrossRefGoogle Scholar
  74. Schlahsa L, Zenk J, Aufderbeck S, Figueiredo C, Blasczyk R (2009) Soluble semaphorin 3A regulates the immune response. Hum Immunol 70:s157CrossRefGoogle Scholar
  75. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  76. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  77. 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 PubMedCrossRefGoogle Scholar
  78. 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 PubMedCrossRefGoogle Scholar
  79. 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 14:1–11CrossRefGoogle Scholar
  80. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 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 99:59–69PubMedCrossRefPubMedCentralGoogle Scholar
  82. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  83. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  84. 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 PubMedCrossRefGoogle Scholar
  85. 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 PubMedCrossRefGoogle Scholar
  86. 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 PubMedCrossRefGoogle Scholar
  87. 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 PubMedCrossRefGoogle Scholar
  88. 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 CrossRefGoogle Scholar
  89. 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 PubMedCrossRefGoogle Scholar
  90. 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 PubMedCrossRefGoogle Scholar
  91. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 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 14:1–8CrossRefGoogle Scholar
  93. 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 PubMedCrossRefGoogle Scholar
  94. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  96. 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 CrossRefGoogle Scholar
  97. 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–S153CrossRefGoogle Scholar
  98. 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 PubMedCrossRefGoogle Scholar
  99. 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 361:321–333PubMedCrossRefGoogle Scholar
  100. Yamamoto M et al (2008) Plexin-A4 negatively regulates T lymphocyte responses. Int Immunol 20:413–420.  https://doi.org/10.1093/intimm/dxn006 PubMedCrossRefGoogle Scholar
  101. Yazdani U, Terman JR (2006) The semaphorins. Genome Biol 7:211.  https://doi.org/10.1186/gb-2006-7-3-211 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 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 CrossRefGoogle Scholar
  103. Yu C, Gershwin ME, Chang C (2014) Diagnostic criteria for systemic lupus erythematosus: a critical review. J Autoimmun 49:10–13CrossRefGoogle Scholar
  104. 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 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Li-Na Liu
    • 1
    • 2
  • Xiao-Mei Li
    • 3
  • Dong-Qing Ye
    • 1
    • 2
  • Hai-Feng Pan
    • 1
  1. 1.Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
  2. 2.Anhui Province Key Laboratory of Major Autoimmune DiseasesHefeiChina
  3. 3.Department of RheumatologyAnhui Provincial HospitalHefeiChina

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