Activins, follistatin and immunoregulation in the epididymis

R. Wijayarathna, M. P. Hedger

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Background: The interface between the epididymis and the immune system is implicated in many male reproductive pathologies.
The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis,
which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions of
the epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodent
models of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductive
tract. Activins are members of the transforming growth factor-b family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunity
in the reproductive tract.
Materials and methods: Our recent research and relevant publications by other researchers identified following a PubMed search
are reviewed.
Results: The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendritic
cells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels of
the activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the cauda
induces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse models
with altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation and
immunoregulation.
Conclusion: The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens
Original languageEnglish
Number of pages9
JournalAndrology
DOIs
Publication statusAccepted/In press - 19 Jul 2019

Cite this

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title = "Activins, follistatin and immunoregulation in the epididymis",
abstract = "Background: The interface between the epididymis and the immune system is implicated in many male reproductive pathologies.The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis,which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions ofthe epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodentmodels of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductivetract. Activins are members of the transforming growth factor-b family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunityin the reproductive tract.Materials and methods: Our recent research and relevant publications by other researchers identified following a PubMed searchare reviewed.Results: The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendriticcells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels ofthe activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the caudainduces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse modelswith altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation andimmunoregulation.Conclusion: The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens",
author = "R. Wijayarathna and Hedger, {M. P.}",
year = "2019",
month = "7",
day = "19",
doi = "10.1111/andr.12682",
language = "English",
journal = "Andrology",
issn = "2047-2919",
publisher = "Wiley-Blackwell",

}

Activins, follistatin and immunoregulation in the epididymis. / Wijayarathna, R.; Hedger, M. P.

In: Andrology, 19.07.2019.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Activins, follistatin and immunoregulation in the epididymis

AU - Wijayarathna, R.

AU - Hedger, M. P.

PY - 2019/7/19

Y1 - 2019/7/19

N2 - Background: The interface between the epididymis and the immune system is implicated in many male reproductive pathologies.The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis,which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions ofthe epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodentmodels of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductivetract. Activins are members of the transforming growth factor-b family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunityin the reproductive tract.Materials and methods: Our recent research and relevant publications by other researchers identified following a PubMed searchare reviewed.Results: The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendriticcells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels ofthe activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the caudainduces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse modelswith altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation andimmunoregulation.Conclusion: The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens

AB - Background: The interface between the epididymis and the immune system is implicated in many male reproductive pathologies.The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis,which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions ofthe epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodentmodels of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductivetract. Activins are members of the transforming growth factor-b family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunityin the reproductive tract.Materials and methods: Our recent research and relevant publications by other researchers identified following a PubMed searchare reviewed.Results: The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendriticcells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels ofthe activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the caudainduces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse modelswith altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation andimmunoregulation.Conclusion: The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens

U2 - 10.1111/andr.12682

DO - 10.1111/andr.12682

M3 - Review Article

JO - Andrology

JF - Andrology

SN - 2047-2919

ER -