Abstract
BackgroundProgrammed 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.MethodsIn 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.ResultsThe 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.ConclusionsThese 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 SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905
Highlights
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
An interesting finding is the uteri from PD-1-/- female mice in the 129svEv-Brd rather Balb/c background are much larger than that of the WT littermates at 2, 2.5 and 3 years of age (Figure 1B and C), indicating that the aged PD1-/- female mice developed endometrial hyperplasia
H&E staining showed that there were numerous glands (Figure 1E) and neovascularizations (Figure 1F) in the aged PD-1-/- uteri (129svEv-Brd background), as compared to WT controls at 2 years of age (Figure 1D). These findings suggested that endometrial hyperplasia was developed in aged PD-1-/- female mice in a 129svEv-Brd background
Summary
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. Co-signaling by B7/CD28 family members regulates the initiation, maintenance, and termination of immune responses. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activated T cells, B cells and myeloid cells [1]. The expression of PD-L1 has been detected in lymphoid organs and in nonlymphoid tissues and was enhanced in several types of tumor cells under inflammation conditions, suggesting that PD-L1 might regulate lymphocyte function at sites of inflammation [15]. The expression of PD-L2, was restricted in activated dendritic cells (DCs), macrophages, monocytes and T cells [16]
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