睾丸支持细胞免疫豁免研究进展及其应用
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摘要
由于独特的免疫豁免能力和有效的固有免疫调控作用,哺乳动物的睾丸拥有特殊的免疫环境。睾丸免疫豁免功能使具有免疫原性的生殖细胞免受免疫系统攻击,而局部固有免疫则在抵御病原微生物感染中发挥作用。睾丸免疫稳态遭到破坏可引起睾丸炎症,甚至男性不育。拥有复杂三维结构的睾丸支持(Sertoli)细胞是睾丸的重要组成细胞,除参与组建精原细胞生长微环境,还通过分泌多种细胞因子和免疫抑制因子调节免疫反应以维持免疫稳态。Sertoli细胞的免疫豁免特性为细胞、组织和器官的替代治疗提供了新思路。文章综述了Sertoli细胞免疫豁免机制的研究进展及其应用。
引文
[1] Iliadou PK,Tsametis C,Kaprara A,et al.The Sertoli cell:Novel clinical potentiality[J].Hormones(Athens),2015,14(4):504-514.
[2] Mruk DD,Cheng CY.The mammalian blood-testis barrier:Its biology and regulation[J].Endocr Rev,2015,36(5):564-591.
[3] Stanton PG.Regulation of the blood-testis barrier[J].Semin Cell Dev Biol,2016,59:166-173.
[4] Wang H,Yuan Q,Sun M,et al.BMP6 regulates proliferation and apoptosis of human Sertoli cells via Smad2/3 and Cyclin D1 pathway and DACH1 and TFAP2A activation[J].Sci Rep,2017,7:45298.
[5] Oliveira PF,Martins AD,Moreira AC,et al.The Warburg effect revisited-lesson from the Sertoli cell[J].Med Res Rev,2015,35(1):126-151.
[6] Tang K,Jin Y,Chen F,et al.Overexpression of C/EBPβ affects the cell cycle regulators and spermatogenesis related genes expression and function of bovine Sertoli cells[J].Reprod Domest Anim,2016,51(4):591-596.
[7] Sheng ZY,Gao N,Wang ZY,et al.Sertoli cells are susceptible to ZIKV infection in mouse testis[J].Front Cell Infect Microbiol,2017,7:272.
[8] Pan Y,Liu Y,Wang L,et al.MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways[J].Oncotarget,2016,7(51):84907-84923.
[9] 娄江涛,魏任雄,余亮亮,等.TGF-β1在大鼠睾丸支持细胞的作用及对紧密连接的影响[J].中华男科学杂志,2017,23(6):510-516.
[10] Hayrabedyan SB,Zasheva DY,Todorova KO.NLRs challenge impacts tight junction claudins in Sertoli cells[J].Folia Med(Plovdiv),2015,57(1):43-48.
[11] Wu D,Huang CJ,Khan FA,et al.SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells[J].Oncotarget,2017,8(35):58430-58442.
[12] Li N,Wong CK,Cheng CY.Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis[J].Asian J Androl,2016,18(5):716-722.
[13] Chen Q,Deng T,Han D.Testicular immunoregulation and spermatogenesis[J].Semin Cell Dev Biol,2016,59:157-165.
[14] Hansen SW,Ohtani K,Roy N,et al.The collectins CL-L1,CL-K1 and CL-P1,and their roles in complement and innate immunity[J].Immunobiology,2016,221(10):1058-1067.
[15] Rokade S,Kishore U,Madan T.Surfactant protein D regulates murine testicular immune milieu and sperm functions[J].Am J Reprod Immunol,2017,77(3):e12629.
[16] Rokade S,Madan T.Testicular expression of SP-A,SP-D and MBL-A is positively regulated by testosterone and modulated by lipopolysaccharide[J].Immunobiology,2016,221(9):975-985.
[17] Zhao RR,Yang XF,Dong J,et al.Toll-like receptor 2 promotes T helper 17 cells response in hepatitis B virus infection[J].Int J Clin Exp Med,2015,8(5):7315-7323.
[18] Wu H,Zhao X,Wang F,et al.Mouse testicular cell type-specific antiviral response against mumps virus replication[J].Front Immunol,2017,8:117.
[19] Wu H,Shi L,Wang Q,et al.Mumps virus-induced innate immune responses in mouse Sertoli and Leydig cells[J].Sci Rep,2016,6:19507.
[20] Campbell L,Raheem I,Malemud CJ,et al.The relationship between NALP3 and autoinflammatory syndromes[J].Int J Mol Sci,2016,17(5):E725.
[21] Wang W,Li G,Wu D,et al.Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1β secretion[J].Nat Commun,2018,9(1):106.
[22] Hayrabedyan S,Todorova K,Jabeen A,et al.Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production[J].Sci Rep,2016,6:18896.
[23] Gao J,Wang X,Wang Y,et al.Murine Sertoli cells promote the development of tolerogenic dendritic cells:A pivotal role of galectin-1[J].Immunology,2016,148(3):253-265.
[24] Rothlin CV,Carrera-Silva EA,Bosurgi L,et al.TAM receptor signaling in immune homeostasis[J].Annu Rev Immunol,2015,33:355-391.
[25] Deng T,Chen Q,Han D.The roles of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites[J].Front Biosci(Landmark Ed),2016,21(2):316-327.
[26] Li N,Liu Z,Zhang Y,et al.Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction[J].Immunol Cell Biol,2015,93(3):311-320.
[27] Kaur G,Vadala S,Dufour JM.An overview of a Sertoli cell transplantation model to study testis morphogenesis and the role of the Sertoli cells in immune privilege[J].Environ Epigenet,2017,3(3):dvx012.
[28] Wang X,Qin J,Zhao RC,et al.Reduced immunogenicity of induced pluripotent stem cells derived from Sertoli cells[J].PLoS One,2014,9(8):e106110.
[29] Luca G,Arato I,Mancuso F,et al.Xenograft of microencapsulated Sertoli cells restores glucose homeostasis in db/db mice with spontaneous diabetes mellitus[J].Xenotransplan-tation,2016,23(6):429-439.
[30] Luca G,Bellezza I,Arato I,et al.Terapeutic potential of microencapsulated Sertoli cells in Huntington disease[J].CNS Neurosci Ther,2016,22(8):686-690.
[2] Mruk DD,Cheng CY.The mammalian blood-testis barrier:Its biology and regulation[J].Endocr Rev,2015,36(5):564-591.
[3] Stanton PG.Regulation of the blood-testis barrier[J].Semin Cell Dev Biol,2016,59:166-173.
[4] Wang H,Yuan Q,Sun M,et al.BMP6 regulates proliferation and apoptosis of human Sertoli cells via Smad2/3 and Cyclin D1 pathway and DACH1 and TFAP2A activation[J].Sci Rep,2017,7:45298.
[5] Oliveira PF,Martins AD,Moreira AC,et al.The Warburg effect revisited-lesson from the Sertoli cell[J].Med Res Rev,2015,35(1):126-151.
[6] Tang K,Jin Y,Chen F,et al.Overexpression of C/EBPβ affects the cell cycle regulators and spermatogenesis related genes expression and function of bovine Sertoli cells[J].Reprod Domest Anim,2016,51(4):591-596.
[7] Sheng ZY,Gao N,Wang ZY,et al.Sertoli cells are susceptible to ZIKV infection in mouse testis[J].Front Cell Infect Microbiol,2017,7:272.
[8] Pan Y,Liu Y,Wang L,et al.MKP-1 attenuates LPS-induced blood-testis barrier dysfunction and inflammatory response through p38 and IκBα pathways[J].Oncotarget,2016,7(51):84907-84923.
[9] 娄江涛,魏任雄,余亮亮,等.TGF-β1在大鼠睾丸支持细胞的作用及对紧密连接的影响[J].中华男科学杂志,2017,23(6):510-516.
[10] Hayrabedyan SB,Zasheva DY,Todorova KO.NLRs challenge impacts tight junction claudins in Sertoli cells[J].Folia Med(Plovdiv),2015,57(1):43-48.
[11] Wu D,Huang CJ,Khan FA,et al.SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells[J].Oncotarget,2017,8(35):58430-58442.
[12] Li N,Wong CK,Cheng CY.Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis[J].Asian J Androl,2016,18(5):716-722.
[13] Chen Q,Deng T,Han D.Testicular immunoregulation and spermatogenesis[J].Semin Cell Dev Biol,2016,59:157-165.
[14] Hansen SW,Ohtani K,Roy N,et al.The collectins CL-L1,CL-K1 and CL-P1,and their roles in complement and innate immunity[J].Immunobiology,2016,221(10):1058-1067.
[15] Rokade S,Kishore U,Madan T.Surfactant protein D regulates murine testicular immune milieu and sperm functions[J].Am J Reprod Immunol,2017,77(3):e12629.
[16] Rokade S,Madan T.Testicular expression of SP-A,SP-D and MBL-A is positively regulated by testosterone and modulated by lipopolysaccharide[J].Immunobiology,2016,221(9):975-985.
[17] Zhao RR,Yang XF,Dong J,et al.Toll-like receptor 2 promotes T helper 17 cells response in hepatitis B virus infection[J].Int J Clin Exp Med,2015,8(5):7315-7323.
[18] Wu H,Zhao X,Wang F,et al.Mouse testicular cell type-specific antiviral response against mumps virus replication[J].Front Immunol,2017,8:117.
[19] Wu H,Shi L,Wang Q,et al.Mumps virus-induced innate immune responses in mouse Sertoli and Leydig cells[J].Sci Rep,2016,6:19507.
[20] Campbell L,Raheem I,Malemud CJ,et al.The relationship between NALP3 and autoinflammatory syndromes[J].Int J Mol Sci,2016,17(5):E725.
[21] Wang W,Li G,Wu D,et al.Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1β secretion[J].Nat Commun,2018,9(1):106.
[22] Hayrabedyan S,Todorova K,Jabeen A,et al.Sertoli cells have a functional NALP3 inflammasome that can modulate autophagy and cytokine production[J].Sci Rep,2016,6:18896.
[23] Gao J,Wang X,Wang Y,et al.Murine Sertoli cells promote the development of tolerogenic dendritic cells:A pivotal role of galectin-1[J].Immunology,2016,148(3):253-265.
[24] Rothlin CV,Carrera-Silva EA,Bosurgi L,et al.TAM receptor signaling in immune homeostasis[J].Annu Rev Immunol,2015,33:355-391.
[25] Deng T,Chen Q,Han D.The roles of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites[J].Front Biosci(Landmark Ed),2016,21(2):316-327.
[26] Li N,Liu Z,Zhang Y,et al.Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction[J].Immunol Cell Biol,2015,93(3):311-320.
[27] Kaur G,Vadala S,Dufour JM.An overview of a Sertoli cell transplantation model to study testis morphogenesis and the role of the Sertoli cells in immune privilege[J].Environ Epigenet,2017,3(3):dvx012.
[28] Wang X,Qin J,Zhao RC,et al.Reduced immunogenicity of induced pluripotent stem cells derived from Sertoli cells[J].PLoS One,2014,9(8):e106110.
[29] Luca G,Arato I,Mancuso F,et al.Xenograft of microencapsulated Sertoli cells restores glucose homeostasis in db/db mice with spontaneous diabetes mellitus[J].Xenotransplan-tation,2016,23(6):429-439.
[30] Luca G,Bellezza I,Arato I,et al.Terapeutic potential of microencapsulated Sertoli cells in Huntington disease[J].CNS Neurosci Ther,2016,22(8):686-690.