title: Decreased PD-1/PD-L1 Expression Is Associated with the Reduction in Mucosal Immunoglobulin A in Mice with Intestinal Ischemia Reperfusion.
abstract: BACKGROUND
  Intestinal ischemia/reperfusion (I/R) disrupts intestinal mucosal integrity and immunoglobulin A (IgA) generation. It has recently been shown that the programmed cell death-1 receptor (PD-1) plays a crucial role in regulating intestinal secreted IgA (sIgA).
  
  
  OBJECTIVE
  To evaluate changes in PD-1 and PD-ligand 1 (PD-L1) expression on Peyer's patches (PP) CD4(+) T cells and to investigate the correlation between PD-1/PD-L1 and intestinal IgA production/mucosal integrity in mice following intestinal I/R.
  
  
  METHODS
  I/R injury was induced by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-1/PD-L1 expression on PP CD4(+) T cells was measured in I/R and sham-operated mice. Additionally, transforming growth factor-β1 (TGF-β1) and interleukin-21 (IL-21) mRNA in CD4(+) T cells and IgA(+) and IgM(+) in PP B cells, as well as intestinal mucosal injury and sIgA levels, were assessed.
  
  
  RESULTS
  PD-1/PD-L1, TGF-β1, and IL-21 expression was down-regulated after intestinal I/R. Furthermore, IgA(+) B cells decreased and IgM(+) B cells increased in mice with intestinal I/R. Importantly, decreased PD-1/PD-L1 expression was correlated with increased mucosal injury and decreased IgA levels, as well as with decreased TGF-β1 and IL-21 expression.
  
  
  CONCLUSIONS
  Intestinal I/R inhibits PD-1/PD-L1 expression on PP CD4(+) T cells, which was associated with an impaired intestinal immune system and mechanical barriers. Our study indicates that PD-1/PD-L1 expression on CD4(+) T cells may be involved in the pathogenesis of intestinal I/R injury.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China.
authors.forename: Xu-Yu
authors.initials: XY
authors.lastname: Zhang
authors.forename: Zi-Meng
authors.initials: ZM
authors.lastname: Liu
authors.forename: Hu-Fei
authors.initials: HF
authors.lastname: Zhang
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Li
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Wen
authors.forename: Jian-Tong
authors.initials: JT
authors.lastname: Shen
authors.forename: Ke-Xuan
authors.initials: KX
authors.lastname: Liu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D007070:Immunoglobulin A / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism; D007378:Interleukins / Q000235:genetics; D007413:Intestinal Mucosa / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007378:Interleukins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000098546:Interleukin-21