Digestive Diseases and Sciences

, Volume 63, Issue 12, pp 3307–3316 | Cite as

Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155 Pathway After Intestinal Ischemia Reperfusion

  • Xu-Yu Zhang
  • Su Guan
  • Hu-Fei Zhang
  • Rui-Yun Li
  • Zi-Meng LiuEmail author
Original Article



To date, mechanisms of intestinal immunoglobulin (Ig) dysfunction following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death 1 (PD-1) is associated with immune responses of lymphocytes.


We aimed to verify the hypothesis that activation of PD-1 may improve intestinal immune dysfunction by regulating IL-10/miR-155 production after intestinal IR injury.


Intestinal I/R injury was induced in mice by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-L1 fusion Ig, anti-interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer’s patches (PP) CD4+ cells were measured. MiR-155 levels, tumor necrosis factor (TNF)-α and IL-1β concentration, and activation-induced cytidine deaminase (AID), a key enzyme for intestinal immune antibodies, in PP tissues were measured, respectively. Importantly, the production and cecal bacteria-binding capacity of IgA and IgM were detected.


Intestinal I/R led to decreased PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then decreased miR-155 levels, and subsequently promoted AID expression and reduced TNF-α, IL-1β concentration. Upregulation of AID improved the disruptions of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal immune defense.


Activation of PD-1 with PD-L1 Ig relieves intestinal immune defensive injury through IL-10/miR-155 pathway following intestinal I/R attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of intestinal barrier and immunity.


Intestinal mucosa Reperfusion injury Programmed cell death 1 receptor microRNA Interleukin-10 



The authors thank Jie Li (Laboratory Animal Center, Sun Yat-sen University) for her help in animal experiments.


The present study was supported by Grants from the Natural Science Foundation of Guangdong Province, China (Grant 2017A030313572 to Xu-Yu Zhang) and grants from the National Natural Science Foundation of China (Grant 81701874 to Zi-meng Liu).

Compliance with ethical standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10620_2018_5282_MOESM1_ESM.docx (838 kb)
Supplementary material 1 (DOCX 837 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Anesthesiology, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina
  2. 2.School of Biology and Biological EngineeringSouth China University of TechnologyGuangzhouChina
  3. 3.Surgical Intensive Care Unit, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

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