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Exploring the role of mononuclear phagocytes in the epididymis.

Da Silva N, Smith TB - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment.This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa.Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

View Article: PubMed Central - PubMed

Affiliation: Massachusetts General Hospital and Harvard Medical School, Division of Nephrology, Center for Systems Biology, Boston, Massachusetts, USA.

ABSTRACT
The onslaught of foreign antigens carried by spermatozoa into the epididymis, an organ that has not demonstrated immune privilege, a decade or more after the establishment of central immune tolerance presents a unique biological challenge. Historically, the physical confinement of spermatozoa to the epididymal tubule enforced by a tightly interwoven wall of epithelial cells was considered sufficient enough to prevent cross talk between gametes and the immune system and, ultimately, autoimmune destruction. The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment. This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa. Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

No MeSH data available.


Related in: MedlinePlus

Localization, phenotype and possible functions of MPs in the steady state murine epididymis. The epididymal epithelium contains principal cells (gray), clear or narrow cells (orange), BCs (red), lymphocytes or halo cells (blue) and MPs (green). In this model, circulating Ly6Chi monocytes and DC precursors constitutively enter the epididymis and differentiate into mature CX3CR1+ CD11c+ F4/80+ Mφs, and CD11c+ CD103+ DCs, respectively. Resident Mφs may also self-renew in situ. MPs could acquire luminal soluble antigens and/or particles directly via extension of intraepithelial processes, or indirectly using conduits created by principal, clear and BCs. Following antigen uptake, migratory CD103+ DCs may migrate to lymph nodes to induce the development of FoxP3+ regulatory T cells (Tregs) in order to regulate tolerance to luminal antigens, or interact locally with resident lymphocytes. In addition, MPs play a major role in the maintenance of the BEB by rapidly removing apoptotic epithelial cells and debris. DCs and Mφs are also involved in the regulation of innate and adaptive immunity when a danger signal is sensed (infection, inflammation), and are also ideally positioned to survey circulating antigens. Our schematic diagram depicts observations made on the MP system in the IS; however, some MP functions might be segment specific. These putative MP functions in the steady state epididymis are largely inspired by studies of the gastrointestinal tract.1113141620 MPs: mononuclear phagocytes; BEB: blood-epididymis barrier; DC: dendritic cell; Mφs: macrophages; BCs: basal cells; IS: initial segment.
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Figure 1: Localization, phenotype and possible functions of MPs in the steady state murine epididymis. The epididymal epithelium contains principal cells (gray), clear or narrow cells (orange), BCs (red), lymphocytes or halo cells (blue) and MPs (green). In this model, circulating Ly6Chi monocytes and DC precursors constitutively enter the epididymis and differentiate into mature CX3CR1+ CD11c+ F4/80+ Mφs, and CD11c+ CD103+ DCs, respectively. Resident Mφs may also self-renew in situ. MPs could acquire luminal soluble antigens and/or particles directly via extension of intraepithelial processes, or indirectly using conduits created by principal, clear and BCs. Following antigen uptake, migratory CD103+ DCs may migrate to lymph nodes to induce the development of FoxP3+ regulatory T cells (Tregs) in order to regulate tolerance to luminal antigens, or interact locally with resident lymphocytes. In addition, MPs play a major role in the maintenance of the BEB by rapidly removing apoptotic epithelial cells and debris. DCs and Mφs are also involved in the regulation of innate and adaptive immunity when a danger signal is sensed (infection, inflammation), and are also ideally positioned to survey circulating antigens. Our schematic diagram depicts observations made on the MP system in the IS; however, some MP functions might be segment specific. These putative MP functions in the steady state epididymis are largely inspired by studies of the gastrointestinal tract.1113141620 MPs: mononuclear phagocytes; BEB: blood-epididymis barrier; DC: dendritic cell; Mφs: macrophages; BCs: basal cells; IS: initial segment.

Mentions: Although the small intestine and the epididymis constitute two radically disparate environments, their respective mucosa may face surprisingly similar immunological challenges. Using the intestine as a model, it seems reasonable that the MPs lining the epididymal duct could be in charge of maintaining the integrity of the epithelial barrier and orchestrating peripheral tolerance to auto-antigenic spermatozoa undergoing maturation; simultaneously, they may fight the pathogens that constantly ascend and threaten the reproductive tract and monitor pathogens circulating in the vasculature (Figure 1).


Exploring the role of mononuclear phagocytes in the epididymis.

Da Silva N, Smith TB - Asian J. Androl. (2015 Jul-Aug)

Localization, phenotype and possible functions of MPs in the steady state murine epididymis. The epididymal epithelium contains principal cells (gray), clear or narrow cells (orange), BCs (red), lymphocytes or halo cells (blue) and MPs (green). In this model, circulating Ly6Chi monocytes and DC precursors constitutively enter the epididymis and differentiate into mature CX3CR1+ CD11c+ F4/80+ Mφs, and CD11c+ CD103+ DCs, respectively. Resident Mφs may also self-renew in situ. MPs could acquire luminal soluble antigens and/or particles directly via extension of intraepithelial processes, or indirectly using conduits created by principal, clear and BCs. Following antigen uptake, migratory CD103+ DCs may migrate to lymph nodes to induce the development of FoxP3+ regulatory T cells (Tregs) in order to regulate tolerance to luminal antigens, or interact locally with resident lymphocytes. In addition, MPs play a major role in the maintenance of the BEB by rapidly removing apoptotic epithelial cells and debris. DCs and Mφs are also involved in the regulation of innate and adaptive immunity when a danger signal is sensed (infection, inflammation), and are also ideally positioned to survey circulating antigens. Our schematic diagram depicts observations made on the MP system in the IS; however, some MP functions might be segment specific. These putative MP functions in the steady state epididymis are largely inspired by studies of the gastrointestinal tract.1113141620 MPs: mononuclear phagocytes; BEB: blood-epididymis barrier; DC: dendritic cell; Mφs: macrophages; BCs: basal cells; IS: initial segment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492049&req=5

Figure 1: Localization, phenotype and possible functions of MPs in the steady state murine epididymis. The epididymal epithelium contains principal cells (gray), clear or narrow cells (orange), BCs (red), lymphocytes or halo cells (blue) and MPs (green). In this model, circulating Ly6Chi monocytes and DC precursors constitutively enter the epididymis and differentiate into mature CX3CR1+ CD11c+ F4/80+ Mφs, and CD11c+ CD103+ DCs, respectively. Resident Mφs may also self-renew in situ. MPs could acquire luminal soluble antigens and/or particles directly via extension of intraepithelial processes, or indirectly using conduits created by principal, clear and BCs. Following antigen uptake, migratory CD103+ DCs may migrate to lymph nodes to induce the development of FoxP3+ regulatory T cells (Tregs) in order to regulate tolerance to luminal antigens, or interact locally with resident lymphocytes. In addition, MPs play a major role in the maintenance of the BEB by rapidly removing apoptotic epithelial cells and debris. DCs and Mφs are also involved in the regulation of innate and adaptive immunity when a danger signal is sensed (infection, inflammation), and are also ideally positioned to survey circulating antigens. Our schematic diagram depicts observations made on the MP system in the IS; however, some MP functions might be segment specific. These putative MP functions in the steady state epididymis are largely inspired by studies of the gastrointestinal tract.1113141620 MPs: mononuclear phagocytes; BEB: blood-epididymis barrier; DC: dendritic cell; Mφs: macrophages; BCs: basal cells; IS: initial segment.
Mentions: Although the small intestine and the epididymis constitute two radically disparate environments, their respective mucosa may face surprisingly similar immunological challenges. Using the intestine as a model, it seems reasonable that the MPs lining the epididymal duct could be in charge of maintaining the integrity of the epithelial barrier and orchestrating peripheral tolerance to auto-antigenic spermatozoa undergoing maturation; simultaneously, they may fight the pathogens that constantly ascend and threaten the reproductive tract and monitor pathogens circulating in the vasculature (Figure 1).

Bottom Line: The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment.This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa.Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

View Article: PubMed Central - PubMed

Affiliation: Massachusetts General Hospital and Harvard Medical School, Division of Nephrology, Center for Systems Biology, Boston, Massachusetts, USA.

ABSTRACT
The onslaught of foreign antigens carried by spermatozoa into the epididymis, an organ that has not demonstrated immune privilege, a decade or more after the establishment of central immune tolerance presents a unique biological challenge. Historically, the physical confinement of spermatozoa to the epididymal tubule enforced by a tightly interwoven wall of epithelial cells was considered sufficient enough to prevent cross talk between gametes and the immune system and, ultimately, autoimmune destruction. The discovery of an intricate arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and macrophages in the murine epididymis suggests that we may have underestimated the existence of a sophisticated mucosal immune system in the posttesticular environment. This review consolidates our current knowledge of the physiology of MPs in the steady state epididymis and speculates on possible interactions between auto-antigenic spermatozoa, pathogens and the immune system by drawing on what is known about the immune system in the intestinal mucosa. Ultimately, further investigation will provide valuable information regarding the origins of pathologies arising as a result of autoimmune or inflammatory responses in the epididymis, including epididymitis and infertility.

No MeSH data available.


Related in: MedlinePlus