信号素4A在RA、MS、SLE、SSc中的研究进展
Research Progress of Semaphorin 4A in RA, MS, SLE, and SSc
DOI: 10.12677/jcpm.2024.34311, PDF,   
作者: 刘 菡：济宁医学院临床医学院，山东 济宁；孙 琳*：济宁市第一人民医院内分泌与代谢科，山东 济宁
关键词: 信号素4A；类风湿性关节炎；多发性硬化；系统性红斑狼疮；系统性硬化；Semaphorin 4A； Rheumatoid Arthritis； Multiple Sclerosis； Systemic Lupus Erythematosus； Systemic Sclerosis
摘要: 信号素4A (Sema4A)是信号蛋白家族的成员，被广泛认为参与免疫应答的所有阶段，是调节T细胞稳态、活化和Th1/2/17分化的关键分子，在T细胞介导的自身免疫性疾病的发病机制中具有重要作用。本文就Sema4A在部分T细胞介导的自身免疫性疾病，如类风湿性关节炎(RA)、多发性硬化(MS)、系统性红斑狼疮(SLE)、系统性硬化(SSc)中的研究进展展开介绍，可有助于寻找此类疾病新的可行性治疗靶标，并为其他自身免疫性疾病发病机制提供新的研究思路。
Abstract: Semaphorin 4A (Sema4A), a member of the semaphorin family, is widely recognized to be involved in all phases of the immune response. It is a key molecule that regulates T cell homeostasis, activation, and Th1/2/17 differentiation, and it plays an important role in the pathogenesis of T cell-mediated autoimmune diseases. This article introduces the research progress of Sema4A in some T cell-mediated autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc), which can help to find new feasible therapeutic targets and provide new research ideas for the pathogenesis of autoimmune diseases.
文章引用：刘菡, 孙琳. 信号素4A在RA、MS、SLE、SSc中的研究进展[J]. 临床个性化医学, 2024, 3(4): 2195-2201. https://doi.org/10.12677/jcpm.2024.34311

参考文献

[1] Fard, D. and Tamagnone, L. (2021) Semaphorins in Health and Disease. Cytokine & Growth Factor Reviews, 57, 55-63. [Google Scholar] [CrossRef] [PubMed]
[2] 欧阳丹, 马远志, 李鑫, 等. 信号素在类风湿关节炎发病机制中作用的研究进展[J]. 中国免疫学杂志, 2024, 40(9): 2001-2005.
[3] Maeda, Y., Tsuda, T., Takeda, Y., Koyama, S., Hayama, Y., Nojima, S., et al. (2019) SEMA4A Promotes Eosinophil Survival and Contributes to Eosinophil-Mediated Allergic Diseases. Allergology International, 68, 274-276. [Google Scholar] [CrossRef] [PubMed]
[4] Carvalheiro, T., Rafael-Vidal, C., Malvar-Fernandez, B., Lopes, A.P., Pego-Reigosa, J.M., Radstake, T.R.D.J., et al. (2020) Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner. International Journal of Molecular Sciences, 21, Article 6965. [Google Scholar] [CrossRef] [PubMed]
[5] Ito, D. and Kumanogoh, A. (2016) The Role of Sema4A in Angiogenesis, Immune Responses, Carcinogenesis, and Retinal Systems. Cell Adhesion & Migration, 10, 692-699. [Google Scholar] [CrossRef] [PubMed]
[6] Cavalcanti, C.A.J., Germoglio, V., de Azevêdo Silva, J., Glesse, N., Vianna, P., Cechim, G., et al. (2019) T-Cell Specific Upregulation of Sema4A as Risk Factor for Autoimmunity in Systemic Lupus Erythematosus and Rheumatoid Arthritis. Autoimmunity, 53, 65-70. [Google Scholar] [CrossRef] [PubMed]
[7] Tang, M.W., Malvar Fernández, B., Newsom, S.P., van Buul, J.D., Radstake, T.R.D.J., Baeten, D.L., et al. (2018) Class 3 Semaphorins Modulate the Invasive Capacity of Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Rheumatology, 57, 909-920. [Google Scholar] [CrossRef] [PubMed]
[8] Wang, L., Song, G., Zheng, Y., Tan, W., Pan, J., Zhao, Y., et al. (2015) Expression of Semaphorin 4A and Its Potential Role in Rheumatoid Arthritis. Arthritis Research & Therapy, 17, Article 227.
[9] Avouac, J., Pezet, S., Vandebeuque, E., Orvain, C., Gonzalez, V., Marin, G., et al. (2021) Semaphorins: From Angiogenesis to Inflammation in Rheumatoid Arthritis. Arthritis & Rheumatology, 73, 1579-1588. [Google Scholar] [CrossRef] [PubMed]
[10] Avouac, J., Vandebeuque, E., Combier, A., Poiroux, L., Steelandt, A., Boisson, M., et al. (2023) Relevance of Circulating Semaphorin 4A for Rheumatoid Arthritis Response to Treatment. Scientific Reports, 13, Article No. 14626. [Google Scholar] [CrossRef] [PubMed]
[11] Toyofuku, T., Yabuki, M., Kamei, J., Kamei, M., Makino, N., Kumanogoh, A., et al. (2007) Semaphorin-4A, an Activator for T-Cell-Mediated Immunity, Suppresses Angiogenesis via Plexin-D1. The EMBO Journal, 26, 1373-1384. [Google Scholar] [CrossRef] [PubMed]
[12] Chapoval, S.P. (2015) Semaphorin 4A as Novel Regulator and Promising Therapeutic Target in Rheumatoid Arthritis. Arthritis Research & Therapy, 17, Article 313.
[13] 刘晓. Sema4A在乳腺癌中的作用和机制的初步研究[D]: [博士学位论文]. 济南: 山东大学, 2019.
[14] Meda, C., Molla, F., De Pizzol, M., Regano, D., Maione, F., Capano, S., et al. (2012) Semaphorin 4A Exerts a Proangiogenic Effect by Enhancing Vascular Endothelial Growth Factor-A Expression in Macrophages. The Journal of Immunology, 188, 4081-4092. [Google Scholar] [CrossRef] [PubMed]
[15] Karussis, D. (2014) The Diagnosis of Multiple Sclerosis and the Various Related Demyelinating Syndromes: A Critical Review. Journal of Autoimmunity, 48, 134-142. [Google Scholar] [CrossRef] [PubMed]
[16] Lotfi, R., Nasiri Kalmarzi, R., Rajabinejad, M., Hasani, S. and Zamani, F. (2021) The Role of Immune Semaphorins in the Pathogenesis of Multiple Sclerosis: Potential Therapeutic Targets. International Immunopharmacology, 95, Article 107556. [Google Scholar] [CrossRef] [PubMed]
[17] Koda, T., Namba, A., Nakatsuji, Y., Niino, M., Miyazaki, Y., Sugimoto, T., et al. (2018) Beneficial Effects of Fingolimod in MS Patients with High Serum Sema4A Levels. PLOS ONE, 13, e0193986. [Google Scholar] [CrossRef] [PubMed]
[18] Volpe, E., Battistini, L. and Borsellino, G. (2015) Advances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis. Mediators of Inflammation, 2015, Article ID: 475158. [Google Scholar] [CrossRef] [PubMed]
[19] Kebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., et al. (2007) Human TH17 Lymphocytes Promote Blood-Brain Barrier Disruption and Central Nervous System Inflammation. Nature Medicine, 13, 1173-1175. [Google Scholar] [CrossRef] [PubMed]
[20] Eiza, N., Garty, M., Staun-Ram, E., Miller, A. and Vadasz, Z. (2022) The Possible Involvement of Sema3a and Sema4a in the Pathogenesis of Multiple Sclerosis. Clinical Immunology, 238, Article 109017. [Google Scholar] [CrossRef] [PubMed]
[21] Kang, Z., Altuntas, C.Z., Gulen, M.F., Liu, C., Giltiay, N., Qin, H., et al. (2010) Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis. Immunity, 32, 414-425. [Google Scholar] [CrossRef] [PubMed]
[22] Arbitman, L., Furie, R. and Vashistha, H. (2022) B Cell-Targeted Therapies in Systemic Lupus Erythematosus. Journal of Autoimmunity, 132, Article 102873. [Google Scholar] [CrossRef] [PubMed]
[23] 谭雪玲, 何仁栋, 向江圆, 等. 信号素4A对SLE患者T细胞功能的影响[J]. 中国免疫学杂志, 2023, 39(4): 822-826.
[24] Sandrin-Garcia, P., Junta, C.M., Fachin, A.L., Mello, S.S., Baião, A.M.T., Rassi, D.M., et al. (2009) Shared and Unique Gene Expression in Systemic Lupus Erythematosus Depending on Disease Activity. Annals of the New York Academy of Sciences, 1173, 493-500. [Google Scholar] [CrossRef] [PubMed]
[25] He, R., Tan, X., Xiang, J., Zhu, J., Jiang, Y., Liu, W., et al. (2022) Semaphorin 4A as a Potential Biomarker for Diagnosis of Systemic Lupus Erythematosus. Immunological Investigations, 52, 104-116. [Google Scholar] [CrossRef] [PubMed]
[26] Lu, N., Li, Y., Zhang, Z., Xing, J., Sun, Y., Yao, S., et al. (2018) Human Semaphorin-4A Drives Th2 Responses by Binding to Receptor Ilt-4. Nature Communications, 9, Article No. 742. [Google Scholar] [CrossRef] [PubMed]
[27] Nakatsuji, Y., Okuno, T., Moriya, M., Sugimoto, T., Kinoshita, M., Takamatsu, H., et al. (2012) Elevation of Sema4A Implicates Th Cell Skewing and the Efficacy of IFN-Β Therapy in Multiple Sclerosis. The Journal of Immunology, 188, 4858-4865. [Google Scholar] [CrossRef] [PubMed]
[28] Kleczynska, W., Jakiela, B., Plutecka, H., Milewski, M., Sanak, M. and Musial, J. (2012) Imbalance between Th17 and Regulatory T-Cells in Systemic Lupus Erythematosus. Folia Histochemica et Cytobiologica, 49, 646-653. [Google Scholar] [CrossRef] [PubMed]
[29] Denton, C.P. and Khanna, D. (2017) Systemic Sclerosis. The Lancet, 390, 1685-1699. [Google Scholar] [CrossRef] [PubMed]
[30] van Bon, L., Cossu, M. and Radstake, T.R.D.J. (2011) An Update on an Immune System That Goes Awry in Systemic Sclerosis. Current Opinion in Rheumatology, 23, 505-510. [Google Scholar] [CrossRef] [PubMed]
[31] Lafyatis, R. and York, M. (2009) Innate Immunity and Inflammation in Systemic Sclerosis. Current Opinion in Rheumatology, 21, 617-622. [Google Scholar] [CrossRef] [PubMed]
[32] Peng, H., Gao, W., Chong, F., Liu, H. and Zhang, J. (2015) Semaphorin 4A Enhances Lung Fibrosis through Activation of Akt via Plexind1 Receptor. Journal of Biosciences, 40, 855-862. [Google Scholar] [CrossRef] [PubMed]
[33] Zhou, Y., Hou, W., Xu, K., Han, D., Jiang, C., Mou, K., et al. (2015) The Elevated Expression of Th17-Related Cytokines and Receptors Is Associated with Skin Lesion Severity in Early Systemic Sclerosis. Human Immunology, 76, 22-29. [Google Scholar] [CrossRef] [PubMed]
[34] Gonçalves, R.S.G., Pereira, M.C., Dantas, A.T., Almeida, A.R.D., Marques, C.D.L., Rego, M.J.B.M., et al. (2017) IL-17 and Related Cytokines Involved in Systemic Sclerosis: Perspectives. Autoimmunity, 51, 1-9. [Google Scholar] [CrossRef] [PubMed]
[35] Onishi, R.M. and Gaffen, S.L. (2010) Interleukin-17 and Its Target Genes: Mechanisms of Interleukin-17 Function in Disease. Immunology, 129, 311-321. [Google Scholar] [CrossRef] [PubMed]
[36] Carvalheiro, T., Affandi, A.J., Malvar‐Fernández, B., Dullemond, I., Cossu, M., Ottria, A., et al. (2019) Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis. Arthritis & Rheumatology, 71, 1711-1722. [Google Scholar] [CrossRef] [PubMed]
[37] Ito, D., Nojima, S., Nishide, M., Okuno, T., Takamatsu, H., Kang, S., et al. (2015) mTOR Complex Signaling through the Sema4a-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells. The Journal of Immunology, 195, 934-943. [Google Scholar] [CrossRef] [PubMed]
[38] Delgoffe, G.M., Woo, S., Turnis, M.E., Gravano, D.M., Guy, C., Overacre, A.E., et al. (2013) Stability and Function of Regulatory T Cells Is Maintained by a Neuropilin-1-Semaphorin-4A Axis. Nature, 501, 252-256. [Google Scholar] [CrossRef] [PubMed]