Immunosuppressive molecules produced by sertoli cells cultured in vitro: Biological effects on lymphocytes

Cesaris, Paola De; Filippini, Antonio; Cervelli, C.; Riccioli, Anna; Starace, Giuseppe; Stefanini, Mario; Ziparo, Elio

doi:10.1016/s0006-291x(05)81596-7

Cited by 82 publications

(50 citation statements)

References 25 publications

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“…Suppression of the immune responses by SCs through the secretion of immunosuppressive factors was determined more than two decades ago. 24,25 Tissue transplantation studies confirmed that SCs provide immune protection resulting in prolonged survival of grafts after cotransplantation with SCs. 26,27 Most cells undergo apoptosis during spermatogenesis, and the cytoplasmic compartments of sperm form residual bodies that are shed before maturation.…”

Section: Immune Privilege In the Testismentioning

confidence: 91%

Testicular defense systems: immune privilege and innate immunity

et al. 2014

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The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation.

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Section: Immune Privilege In the Testismentioning

confidence: 91%

Testicular defense systems: immune privilege and innate immunity

et al. 2014

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“…SeC inhibit the humoral and T-cell response thanks to their ability to secrete factors that block T lymphocyte proliferation and interleukin (IL)-2 production [90,91]. Moreover, FASL (CD95L) expressed on SeC might interact with the FAS receptor (CD95) on the T cell surface, inducing apoptosis of lymphocytes [92].…”

Section: The Immunomodulatory Properties Of Secmentioning

confidence: 99%

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Chiappalupi

Salvadori

Luca

et al. 2017

JFMK

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Duchenne muscular dystrophy (DMD) is a lethal X-linked pathology due to lack of dystrophin and characterized by progressive muscle degeneration, impaired locomotion and premature death. The chronic presence of inflammatory cells, fibrosis and fat deposition are hallmarks of DMD muscle tissue. Many different therapeutic approaches to DMD have been tested, including cell-based and gene-based approaches, exon skipping, induction of expression of the dystrophin paralogue, utrophin, and, most recently the application of the CASPR/Cas9 genome editing system. However, corticosteroid treatment remains the gold standard therapy, even if corticosteroids have shown multiple undesirable side effects. Sertoli cells (SeC) have long been known for their ability to produce immunomodulatory and trophic factors, and have been used in a plethora of experimental models of disease. Recently, microencapsulated porcine SeC (MC-SeC) injected intraperitoneally in dystrophic mice produced morphological and functional benefits in muscles thanks to their release into the circulation of anti-inflammatory factors and heregulin β1, a known inducer of utrophin expression, thus opening a new avenue in the treatment of DMD. In order to stress the potentiality of the use of MC-SeC in the treatment of DMD, here, we examine the principal therapeutic approaches to DMD, and the properties of SeC (either nude or encapsulated into alginate-based microcapsules) and their preclinical and clinical use. Finally, we discuss the potential and future development of this latter approach.Keywords: Duchenne muscular dystrophy; therapeutic approaches; Sertoli cell; muscle inflammation; myopathies; encapsulation; biomaterials Duchenne Muscular Dystrophy (DMD)Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. Muscular dystrophies are a group of inherited muscle diseases characterized by mutations in specific genes and resulting in muscle degeneration, impaired locomotion and premature death [1,2]. DMD is an X-linked recessive pathology caused by mutations in the dystrophin gene (DMD) usually resulting in the complete absence of this protein. Dystrophin is an essential component of the dystrophin-associated protein complex (DAPC) at the sarcolemma, a complex that ensures the structural and functional integrity of the myofibers during contraction representing a mechanical link between the intracellular cytoskeleton and the extracellular matrix. Absence of dystrophin or other components of the DAPC compromises the integrity of the DAPC itself leading to a susceptibility of myofibers to degeneration

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“…Several in vitro cell culture experiments have demonstrated that SCs secrete molecules that inhibit the proliferation of both B and T lymphocytes (Wyatt et al 1988, Selawry et al 1991, De Cesaris et al 1992. Moreover, detailed analysis of the cellular infiltrate in rejected SC/islet co-grafts, using selective markers for the different immune cells, revealed the presence of high numbers of CD4 T-cells, CD8 T-cells, and macrophages (Dufour et al 2008b).…”

Section: Production Of Immunoprotective Factors By Sertoli Cellsmentioning

confidence: 99%

“…Cultured SCs have been shown to secrete factors that inhibit T-cell proliferation by arresting them in G 1 phase of the cell cycle (Wyatt et al 1988, Selawry et al 1991, De Cesaris et al 1992. The blockade of lymphocyte proliferation was associated with a decrease in the production of interleukin-2 (IL2), which could not be overcome with the addition of exogenous IL2 suggesting that some unidentified factor(s) secreted by the SCs suppressed both IL2 production as well as the responsiveness of the lymphocytes to exogenous IL2 (Selawry et al 1991, De Cesaris et al 1992.…”

Section: Sertoli Cell Influence On T-cell Responsesmentioning

confidence: 99%

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Mital¹,

Kaur²,

2010

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The testis as an immune-privileged site allows long-term survival of allogeneic and xenogeneic transplants. Testicular Sertoli cells (SCs) play a major role in this immunoprotection and have been used to create an ectopic immune-privileged environment that prolongs survival of co-transplanted allogeneic and xenogeneic cells, including pancreatic islets and neurons. Extended survival of such grafts testifies to the immunoprotective properties of SCs. However, there is still variability in the survival rates of the co-grafted cells and rarely are 100% of the grafts protected. This emphasizes the need to learn more about what is involved in creating the optimal immunoprotective milieu. Several parameters including organization of the SCs into tubule-like structures and the production of immunomodulatory factors by SCs, specifically complement inhibitors, cytokines, and cytotoxic lymphocyte inhibitors, are likely important. In addition, an intricate interplay between several of these factors may be responsible for providing the most ideal environment for protection of the co-transplants by SCs. In this review, we will also briefly describe a novel use for the immune-privileged abilities of SCs; engineering them to deliver therapeutic proteins for the treatment of diseases like diabetes and Parkinson's disease. In conclusion, further studies and more detailed analysis of the mechanisms involved in creating the immune-protective environment by SCs may make their application in co-transplantation and as engineered cells clinically feasible.

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Immunosuppressive molecules produced by sertoli cells cultured in vitro: Biological effects on lymphocytes

Cited by 82 publications

References 25 publications

Testicular defense systems: immune privilege and innate immunity

Testicular defense systems: immune privilege and innate immunity

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

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