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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

MPs in the proximal mouse epididymis. CD11c+ and CX3CR1+ MPs are abundant in the murine epididymis. This partial view of the most proximal region of a section of CD11c-EYFP mouse epididymis reveals CD11c+ DCs and Mφs. CD11c+ MPs are present in the peritubular region as well as in the interstitium and the capsule (arrowhead) that wraps the epididymis. In the IS (brightest area), which is the most proximal epididymal segment, CD11c+ (and CX3CR1+) intraepithelial Mφs extend dendritic processes toward the apical side of the epithelium, suggesting that this particular subset of MPs is in charge of directly surveying the luminal content, possibly in a segment-specific manner. Scale bars = 50 μm, L: lumen; MPs: mononuclear phagocytes; DCs: dendritic cell; Mφs: macrophages; IS: initial segment.
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Figure 2: MPs in the proximal mouse epididymis. CD11c+ and CX3CR1+ MPs are abundant in the murine epididymis. This partial view of the most proximal region of a section of CD11c-EYFP mouse epididymis reveals CD11c+ DCs and Mφs. CD11c+ MPs are present in the peritubular region as well as in the interstitium and the capsule (arrowhead) that wraps the epididymis. In the IS (brightest area), which is the most proximal epididymal segment, CD11c+ (and CX3CR1+) intraepithelial Mφs extend dendritic processes toward the apical side of the epithelium, suggesting that this particular subset of MPs is in charge of directly surveying the luminal content, possibly in a segment-specific manner. Scale bars = 50 μm, L: lumen; MPs: mononuclear phagocytes; DCs: dendritic cell; Mφs: macrophages; IS: initial segment.

Mentions: In humans and rodents, the pseudostratified epithelium that lines the epididymal duct is composed of several types of cells, including principal cells, clear/narrow cells, and basal cells (BCs). Altogether, these cells are in charge of creating a succession of microenvironments in which sperm mature and are stored.363738394041 Sperm maturation and storage involves a finely tuned sequence of complex interactions between the epithelium, the luminal fluid, and spermatozoa. Alongside epithelial cells, cells of the immune system were identified in the epididymis several decades ago, including lymphocytes (most likely referred to as “halo cells”) and Mφs.442434445 Both Mφs and lymphocytes have been shown to respond to changes in the epididymis initiated by aging, vasectomy and infections.346474849 However, these discoveries provide not more than a superficial view of the increasingly complex mucosal immune system composed of many phenotypically, morphologically and functionally distinct subsets of lymphoid and myeloid cells, including MPs, which maintain constant interactions. In order to unravel the immunophysiology of the epididymis, it is now vital to unambiguously identify each subset of immune cell and determine how they interact with their environment. Fortunately, immunologists have developed a battery of powerful tools to study immune cells in other organ systems, thus introducing new perspectives to reproductive biologists. Among those tools, two lines of transgenic mice (CD11c-EYFP50 and CX3CR1-GFP51) have allowed us to illuminate an extensive network of DCs and Mφs in the mouse epididymis1 (Figure 2). CD11c (integrin alpha X) and CX3CR1 (a G-protein coupled chemokine receptor) are expressed by several subsets of Mφs and DCs.


Exploring the role of mononuclear phagocytes in the epididymis.

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

MPs in the proximal mouse epididymis. CD11c+ and CX3CR1+ MPs are abundant in the murine epididymis. This partial view of the most proximal region of a section of CD11c-EYFP mouse epididymis reveals CD11c+ DCs and Mφs. CD11c+ MPs are present in the peritubular region as well as in the interstitium and the capsule (arrowhead) that wraps the epididymis. In the IS (brightest area), which is the most proximal epididymal segment, CD11c+ (and CX3CR1+) intraepithelial Mφs extend dendritic processes toward the apical side of the epithelium, suggesting that this particular subset of MPs is in charge of directly surveying the luminal content, possibly in a segment-specific manner. Scale bars = 50 μm, L: lumen; MPs: mononuclear phagocytes; DCs: dendritic cell; Mφs: macrophages; IS: initial segment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: MPs in the proximal mouse epididymis. CD11c+ and CX3CR1+ MPs are abundant in the murine epididymis. This partial view of the most proximal region of a section of CD11c-EYFP mouse epididymis reveals CD11c+ DCs and Mφs. CD11c+ MPs are present in the peritubular region as well as in the interstitium and the capsule (arrowhead) that wraps the epididymis. In the IS (brightest area), which is the most proximal epididymal segment, CD11c+ (and CX3CR1+) intraepithelial Mφs extend dendritic processes toward the apical side of the epithelium, suggesting that this particular subset of MPs is in charge of directly surveying the luminal content, possibly in a segment-specific manner. Scale bars = 50 μm, L: lumen; MPs: mononuclear phagocytes; DCs: dendritic cell; Mφs: macrophages; IS: initial segment.
Mentions: In humans and rodents, the pseudostratified epithelium that lines the epididymal duct is composed of several types of cells, including principal cells, clear/narrow cells, and basal cells (BCs). Altogether, these cells are in charge of creating a succession of microenvironments in which sperm mature and are stored.363738394041 Sperm maturation and storage involves a finely tuned sequence of complex interactions between the epithelium, the luminal fluid, and spermatozoa. Alongside epithelial cells, cells of the immune system were identified in the epididymis several decades ago, including lymphocytes (most likely referred to as “halo cells”) and Mφs.442434445 Both Mφs and lymphocytes have been shown to respond to changes in the epididymis initiated by aging, vasectomy and infections.346474849 However, these discoveries provide not more than a superficial view of the increasingly complex mucosal immune system composed of many phenotypically, morphologically and functionally distinct subsets of lymphoid and myeloid cells, including MPs, which maintain constant interactions. In order to unravel the immunophysiology of the epididymis, it is now vital to unambiguously identify each subset of immune cell and determine how they interact with their environment. Fortunately, immunologists have developed a battery of powerful tools to study immune cells in other organ systems, thus introducing new perspectives to reproductive biologists. Among those tools, two lines of transgenic mice (CD11c-EYFP50 and CX3CR1-GFP51) have allowed us to illuminate an extensive network of DCs and Mφs in the mouse epididymis1 (Figure 2). CD11c (integrin alpha X) and CX3CR1 (a G-protein coupled chemokine receptor) are expressed by several subsets of Mφs and DCs.

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