title: The development of endometrial hyperplasia in aged PD-1-deficient female mice.
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.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5809067461223905.
authors.forename: Guoning
authors.initials: G
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Dayan
authors.initials: D
authors.lastname: Cao
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, People's Republic of China. yongwench@163.com.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004714:Endometrial Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse