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The development of endometrial hyperplasia in aged PD-1-deficient female mice.

Guo G, Li H, Cao D, Chen Y - Diagn Pathol (2014)

Bottom Line: Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively.Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People's Republic of China. yongwench@163.com.

ABSTRACT

Background: Programmed death-1 (PD-1, Pdcd1)-deficient mice develop different types of autoimmune diseases depending on the mouse strain but its role in uterus development has not been reported.

Methods: In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in uterine tissues from aged WT mice in a 129svEv-Brd background was analyzed by immunohistochemistry and the uterine morphology between WT and PD-1-/- mice was compared by hematoxylin and eosin staining.

Results: The aged PD-1-/- female mice in a 129svEv-Brd rather than Balb/c background develop endometrial hyperplasia. H&E staining showed an increase in the number of glands, neovascularization and an extremely large luminal cavity in aged PD-1-/- uteri. Immunohistochemical assay showed that the expression of PD-1 was observed in glandular/luminal epithelium and cells infiltrating the stroma. Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively. Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.

Conclusions: These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.

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The characteristic and anatomic distribution of PD-1 ligands, PD-L1 and PD-L2, in uteri from 2-year old WT mice was detected by immunohistochemistry. (A) Mouse IgG1 isotype control antibodies showed no positive staining; (B) PD-L1 positive cells were observed in the glandular/luminal epithelium; (C) PD-L1 positive cells were observed in the endothelium and cells infiltrated stroma; (D) The PD-L2 expression was absent in blood capillary; (E) The PD-L2 positive cells were observed in the glandular/luminal epithelium; and (F) PD-L2 positive cells were observed infiltrating the stroma. ▲ indicates the glandular epithelium; *indicates the luminal cavity; ◆ indicated blood capillary. The arrows indicate positive endothelial cells and arrow head showed infiltrated cells that are positive for PD-L1 or PD-L2. Scale bar = 20 μm. N = 4 of each group.
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Figure 4: The characteristic and anatomic distribution of PD-1 ligands, PD-L1 and PD-L2, in uteri from 2-year old WT mice was detected by immunohistochemistry. (A) Mouse IgG1 isotype control antibodies showed no positive staining; (B) PD-L1 positive cells were observed in the glandular/luminal epithelium; (C) PD-L1 positive cells were observed in the endothelium and cells infiltrated stroma; (D) The PD-L2 expression was absent in blood capillary; (E) The PD-L2 positive cells were observed in the glandular/luminal epithelium; and (F) PD-L2 positive cells were observed infiltrating the stroma. ▲ indicates the glandular epithelium; *indicates the luminal cavity; ◆ indicated blood capillary. The arrows indicate positive endothelial cells and arrow head showed infiltrated cells that are positive for PD-L1 or PD-L2. Scale bar = 20 μm. N = 4 of each group.

Mentions: The expression of the PD-1ligands, PD-L1 and PD-L2, in the aged uteri from WT mice was also detected by immunohistochemistry. Similar to PD-1, the expression of PD-L1 was also observed in glandular/luminal epithelium (Figure 4B). Cells infiltrating the stroma and some endothelial cells were also positive for PD-L1 (Figure 4C). In contrast, the expression of PD-L2 was absent in blood endothelium (Figure 4D) but present in glandular/luminal endothelium and cells infiltrating the stroma (Figure 4E and F).


The development of endometrial hyperplasia in aged PD-1-deficient female mice.

Guo G, Li H, Cao D, Chen Y - Diagn Pathol (2014)

The characteristic and anatomic distribution of PD-1 ligands, PD-L1 and PD-L2, in uteri from 2-year old WT mice was detected by immunohistochemistry. (A) Mouse IgG1 isotype control antibodies showed no positive staining; (B) PD-L1 positive cells were observed in the glandular/luminal epithelium; (C) PD-L1 positive cells were observed in the endothelium and cells infiltrated stroma; (D) The PD-L2 expression was absent in blood capillary; (E) The PD-L2 positive cells were observed in the glandular/luminal epithelium; and (F) PD-L2 positive cells were observed infiltrating the stroma. ▲ indicates the glandular epithelium; *indicates the luminal cavity; ◆ indicated blood capillary. The arrows indicate positive endothelial cells and arrow head showed infiltrated cells that are positive for PD-L1 or PD-L2. Scale bar = 20 μm. N = 4 of each group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4066824&req=5

Figure 4: The characteristic and anatomic distribution of PD-1 ligands, PD-L1 and PD-L2, in uteri from 2-year old WT mice was detected by immunohistochemistry. (A) Mouse IgG1 isotype control antibodies showed no positive staining; (B) PD-L1 positive cells were observed in the glandular/luminal epithelium; (C) PD-L1 positive cells were observed in the endothelium and cells infiltrated stroma; (D) The PD-L2 expression was absent in blood capillary; (E) The PD-L2 positive cells were observed in the glandular/luminal epithelium; and (F) PD-L2 positive cells were observed infiltrating the stroma. ▲ indicates the glandular epithelium; *indicates the luminal cavity; ◆ indicated blood capillary. The arrows indicate positive endothelial cells and arrow head showed infiltrated cells that are positive for PD-L1 or PD-L2. Scale bar = 20 μm. N = 4 of each group.
Mentions: The expression of the PD-1ligands, PD-L1 and PD-L2, in the aged uteri from WT mice was also detected by immunohistochemistry. Similar to PD-1, the expression of PD-L1 was also observed in glandular/luminal epithelium (Figure 4B). Cells infiltrating the stroma and some endothelial cells were also positive for PD-L1 (Figure 4C). In contrast, the expression of PD-L2 was absent in blood endothelium (Figure 4D) but present in glandular/luminal endothelium and cells infiltrating the stroma (Figure 4E and F).

Bottom Line: Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively.Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People's Republic of China. yongwench@163.com.

ABSTRACT

Background: Programmed death-1 (PD-1, Pdcd1)-deficient mice develop different types of autoimmune diseases depending on the mouse strain but its role in uterus development has not been reported.

Methods: In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in uterine tissues from aged WT mice in a 129svEv-Brd background was analyzed by immunohistochemistry and the uterine morphology between WT and PD-1-/- mice was compared by hematoxylin and eosin staining.

Results: The aged PD-1-/- female mice in a 129svEv-Brd rather than Balb/c background develop endometrial hyperplasia. H&E staining showed an increase in the number of glands, neovascularization and an extremely large luminal cavity in aged PD-1-/- uteri. Immunohistochemical assay showed that the expression of PD-1 was observed in glandular/luminal epithelium and cells infiltrating the stroma. Fluorescent double staining demonstrated that PD-1 expresses on CD68+ macrophages, CD3+ T cells, CD16+ monocytes, CD56+ NK cells and CK-18+ epithelial cells, respectively. Additionally, PD-1 co-expresses with vascular endothelial growth factor (VEGF), and PD-1 deficiency resulted in an accumulation of glandular/luminal epithelium derived VEGF, which accelerates the expression of the proliferation-associated protein, proliferating cell nuclear antigen (PCNA), and thus potentially lead to epithelial proliferation in aged PD-1-/- uteri.

Conclusions: These findings showed that PD-1 deficiency augments luminal epithelial cell proliferation probably through induced VEGF secretion, suggesting PD-1 plays an important role in controlling the growth and differentiation of the uterine epithelium.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.

Show MeSH
Related in: MedlinePlus