Mechanisms of testicular immune privilege

Wang, Tao; Feng, Xueying; Han, Daishu

doi:10.1007/s11515-011-1010-4

Cited by 6 publications

(5 citation statements)

References 118 publications

(117 reference statements)

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“…SCs secrete several immunoprotective factors that block B‐ and T‐lymphocyte proliferation, thereby suppressing IL‐2 production (Selawry et al ., ; De Cesaris et al ., ; Wang et al ., ). Critical for testis‐related immunoprivilege are macrophages and lymphocytes, the main components of the interstitial cell population.…”

Section: The Sertoli Cells: Basic Aspects and Functionmentioning

confidence: 97%

“…Critical for testis‐related immunoprivilege are macrophages and lymphocytes, the main components of the interstitial cell population. In particular, macrophages are oriented toward an M2 cell phenotype (80% of the macrophage population) as opposed to a 20% M1 cell phenotype that prevails in other tissues (Wang et al ., ). The mechanisms regulating the balance between M1 and M2 macrophages remain unclear, but it is likely that SCs, together with Leydig cells, hold the ability to produce and secrete factors that induce a M1 shift toward the M2 cell phenotype.…”

Section: The Sertoli Cells: Basic Aspects and Functionmentioning

confidence: 97%

“…In fact, Wang et al . showed that Toll‐like receptors present on the SC membrane can contrast many bacteria and viruses (Wang et al ., ). Recently, Ziparo et al .…”

Section: The Sertoli Cells: Basic Aspects and Functionmentioning

confidence: 97%

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Sertoli cells for cell transplantation: pre‐clinical studies and future perspectives

et al. 2018

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Sertoli cells are located in the testes where they control several key functions in spermatogenesis. Over the past 30 years, Sertoli cells have been upgraded from a simple scaffold-like structural system to a dynamic functional system of intercellular support that delivers potent immunomodulatory and trophic factors. Since the discovery of new Sertoli cell secretory products, these cells have been utilized in experimental cell transplantation and co-transplantation protocols aimed at treating both chronic inflammatory and degenerative disorders. For these reasons, this work reviews the application of both naked and microencapsulated Sertoli cells used in cell transplantation studies of several chronic or autoimmune diseases such as diabetes mellitus, Laron dwarfism, and Duchenne muscular dystrophy and in studies aimed at the prevention of skin allograft rejection.

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Section: The Sertoli Cells: Basic Aspects and Functionmentioning

confidence: 97%

Section: The Sertoli Cells: Basic Aspects and Functionmentioning

confidence: 97%

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Sertoli cells for cell transplantation: pre‐clinical studies and future perspectives

et al. 2018

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“…Moreover, it has been demonstrated that TGF-β with IL-10 and activin-A, released by SeC, contribute to modulate the immune cell response in the testis, stimulating immune cells involved in the tolerogenic response, such as M2 (anti-inflammatory) macrophages, and Th2 and Treg cells [95]. Accordingly, most macrophages located in the testis show an M2 phenotype [96]. Recently, a soluble form of JAGGED1 (JAG1), which induces the generation of Treg cells, has been reported to be secreted by SeC [97].…”

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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“…The testis is a remarkable immunoprivileged site. However, infections of the testis are usually overcome, suggesting that an active and efficient immune response against pathogens can be locally generated [2]. Growing evidence shows that the local testicular somatic cell-initiated innate immunity plays an important role in the defense against invading microbial pathogens [3].…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 3-Initiated Antiviral Responses in Mouse Male Germ Cells In Vitro1

Wang

Zhang

Chen

et al. 2012

Biology of Reproduction

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The testis is an immunoprivileged site where local cell-initiated innate immunity plays a crucial role in antimicrobial responses. Toll-like receptors (TLRs) mediate innate immune responses in testicular somatic cells. Although several TLRs are expressed in some stages of male germ cells, the potential role of TLRs in triggering antimicrobial responses in the germ cells has yet to be exclusively studied. The current study demonstrates that TLR3 is constitutively expressed in spermatogonia and spermatocytes and can be activated by a synthetic double-strained RNA analog, polyinosinic-polycytidylic acid. TLR3 activation in these male germ cells up-regulates the expression of proinflammatory cytokines, such as interleukin IL1B, IL6, and tumor necrosis factor alpha, through activation of nuclear factor kappa B; it also induces production of type 1 interferons (IFNA and IFNB) through the activation of IFN regulatory factor 3. In addition, TLR3 activation increases the production of two major antiviral proteins, namely, double-stranded RNA-activated protein kinase and MX1 protein, by germ cells. Data in this article describe an antiviral response of male germ cells through the activation of TLR3 in vitro.

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Mechanisms of testicular immune privilege

Cited by 6 publications

References 118 publications

Sertoli cells for cell transplantation: pre‐clinical studies and future perspectives

Sertoli cells for cell transplantation: pre‐clinical studies and future perspectives

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

Toll-Like Receptor 3-Initiated Antiviral Responses in Mouse Male Germ Cells In Vitro1

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