Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2022; 28(26): 3164-3176
Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3164
Bifidobacterium infantis regulates the programmed cell death 1 pathway and immune response in mice with inflammatory bowel disease
Lin-Yan Zhou, Ying Xie, Yan Li
Lin-Yan Zhou, Ying Xie, Yan Li, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Author contributions: Zhou LY obtained funding, processed the samples, analyzed the raw data, and wrote manuscript; Xie Y processed the samples, obtained and managed data; Li Y conceived the study protocol, critically revised the manuscript, and approved the final version.
Supported by the Doctoral Start-up Foundation of Liaoning Province, No. 2021-BS-114.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Shengjing Hospital of China Medical University.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals, No. 2017PS353K.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan Li, PhD, Chief Doctor, Professor, Department of Gastroenterology, Shengjing Hospital of China Medical University, No. 36 Sanhao Road, Heping District, Shenyang 110004, Liaoning Province, China. liy@sj-hospital.org
Received: December 6, 2021
Peer-review started: December 6, 2021
First decision: January 8, 2022
Revised: January 12, 2022
Accepted: June 16, 2022
Article in press: June 16, 2022
Published online: July 14, 2022
Processing time: 218 Days and 19 Hours
ARTICLE HIGHLIGHTS
Research background

The immune-inflammatory response plays an important role in the pathogenesis and development of inflammatory bowel disease (IBD). Bifidobacterium infantis (B. infantis) can repair the acute intestinal mucosal injury and maintain autoimmune tolerance in mice with IBD.

Research motivation

The specific mechanism of action of B. infantis in the treatment of IBD is unclear. Understanding this underlying mechanism will help in the treatment of IBD.

Research objectives

To explore if B. infantis can promote regulatory T cell Treg differentiation through the programmed cell death 1 (PD-1)/PD ligand (PD-L1) pathway to promote the expression of forkhead box protein 3 (Foxp3), interleukin (IL)-10 and transforming growth factor β (TGF-β) 1, and reduce the inflammatory response.

Research methods

We blocked the expression of PD-L1 in the intestine and performed western blotting and real-time qPCR to observe the effects of B. infantis on PD-1, Foxp3, IL-10, and TGF-β1. Flow cytometry was used to examine the changes in the differentiation of CD4+, CD25+, and Foxp3+ cells in the blood and spleen after blocking PD-L1.

Research results

PD-L1 inhibition reduced the promoting effects of B. infantis on intestinal PD-1, Foxp3, IL-10, and TGF-β1. The promoting effect of B. infantis on the differentiation of CD4+, CD25+, and Foxp3+ cells was also reduced.

Research conclusions

B. infantis mediates Foxp3 expression through the PD-1/PD-L1 pathway, thereby promoting Treg differentiation and improving IL-10 and TGF-β1 expression to reduce the immune and inflammatory response in IBD. B. infantis may act as a therapeutic agent for IBD.

Research perspectives

To explore the mechanism of action of B. infantis in the treatment of IBD at the cellular level. Further experiments are essential to determine whether B. infantis inhibits the immune response through the PD-1/PD-L1 pathway in the patients with IBD.