Decreased PD-1/PD-L1 Expression Is Associated with the Reduction in Mucosal Immunoglobulin A in Mice with Intestinal Ischemia Reperfusion

• Published in: Digestive diseases and sciences Vol. 60; no. 9; pp. 2662 - 2669
• Main Authors: Zhang, Xu-Yu, Liu, Zi-Meng, Zhang, Hu-fei, Li, Yun-Sheng, Wen, Shi-Hong, Shen, Jian-Tong, Liu, Ke-Xuan
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2015; Springer; Springer Nature B.V
• Subjects: Animals; Apoptosis; B-Lymphocytes - metabolism; B7-H1 Antigen - metabolism; Biochemistry; CD4-Positive T-Lymphocytes - metabolism; Gastroenterology; Hepatology; Immunoglobulin A - metabolism; Immunoglobulin M - metabolism; Interleukins - genetics; Intestinal Mucosa - blood supply; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Ischemia; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Oncology; Original Article; Peyer's Patches - pathology; Programmed Cell Death 1 Receptor - metabolism; Reperfusion Injury - metabolism; RNA, Messenger - metabolism; Transforming Growth Factor beta1 - genetics; Transplant Surgery; Programmed cell death 1 receptor; Immunoglobulin class switching; Immunoglobulin A; Intestinal mucosa; Reperfusion injury
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-015-3684-y

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). Aims 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.