, 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


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.


Semaphorin-3A Therapeutic agent Autoimmune diseases 



Autoimmune diseases


Alpha B-crystallin


B-cell activating factor


B regulatory cells


Collagen-induced arthritis


Central nervous system


Cytosine-phosphodiester-guanine oligodeoxynucleotides


Disease Activity Score 28-joint count C reactive protein


Dendritic cells


Diffuse systemic sclerosis


Experimental autoimmune encephalomyelitis


Forkhead box P3


Interleukin 2


Interleukin 10


Interleukin 17




Limited systemic sclerosis


Lupus glomerulonephritis


Myelin binding glycoprotein


Ras/mitogen-activated protein kinase


Oligodendrocyte glycoprotein


Multiple sclerosis






Oligodendrocyte precursor cell


Peripheral blood mononuclear cells




Rheumatoid arthritis


Receiver operating characteristic


Relapsing–remitting multiple sclerosis




Systemic lupus erythematosus


Systemic sclerosis


Transforming growth factor beta


Helper T-cell type 1


Helper T-cell type 17


Tumor necrosis factor


Regulatory T cells


Vascular endothelial growth factor


Vascular endothelial growth factor receptor



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.


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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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