Circulating and intestinal regulatory T cells in inflammatory bowel disease: A systemic review and meta-analysis

Abstract

Regulatory T cells (Tregs) play an important immunosuppressive role in inflammatory bowel disease (IBD). However, findings on the quantitative and functional changes of intestinal and circulating Tregs in patients with IBD are rather contradictory. We therefore conducted a meta-analysis on this issue. The pooled effect was assessed using the standardized mean difference (SMD) with a 95% confidence interval (CI), and subgroup analyses were performed to investigate heterogeneity. This analysis included 764 IBD (402 UC and 362 CD) patients and 341 healthy controls (HCs) pooled from 17 eligible studies. The percentage of circulating Tregs was significantly decreased in active IBD patients compared to HCs (SMD = −0.95, p < 0.001) and inactive IBD patients (SMD = −0.80, p < 0.001). There was no difference in the percentage of circulating Tregs between inactive IBD patients and HCs. The suppressive function of circulating Tregs was impaired in active IBD patients according to limited data (SMD = −0.75, p = 0.02). Besides, the percentage of intestinal Tregs was significantly higher in inflamed regions than in non-inflamed regions (SMD = 0.85, p < 0.001). Our study quantitatively summarized the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.

PLAIN LANGUAGE SUMMARY

Inflammatory bowel disease is a group of diseases in which the intestines are repeatedly inflamed. Regulatory T cells are a subset of immune cells that have been found to migrate from the blood and lymphoid tissues into the intestine to act as a suppressor of inflammation in inflammatory bowel disease. However, previous research on changes in the amount and function of regulatory T cells in the blood and intestine of patients with inflammatory bowel disease revealed inconsistent results. Therefore, we used a “meta-analysis” approach to integrate the results of previous studies to obtain an overall picture of Changes in regulatory T cell percentages and function. We found that patients with active inflammatory bowel disease had a lower proportion of blood regulatory T cells and a poorer ability to suppress inflammation compared to healthy individuals. In the intestine of patients with inflammatory bowel disease, a higher proportion of regulatory T cells are found in inflamed sites than in non-inflamed sites. However, compared to other intestinal inflammatory diseases, such as intestinal tuberculosis, patients with inflammatory bowel disease have a lower tendency of elevated proportions of intestinal regulatory T cells. In some ways, our study quantitatively summarized the conflicting results of the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.

Graphical_Abstract

Keywords:

• Immune tolerance
• inflammatory bowel disease
• meta-analysis
• regulatory T cells

Authors’ contributions

All authors contributed to the study conception and design. Conceptualization and Supervision were performed by Yan Zhang. Material preparation and data collection were performed by Pingrun Chen and Yi Yang. Analysis and Validation were performed by Shihao Duan and Yubin Cao. The first draft of the manuscript was written by Shihao Duan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Disclosure statement

The authors report no conflict of interest. The graphical abstract was created with BioRender.com.

Data availability statement

All data generated or analyzed during this study are included in this article and its supplementary information files.

Additional information

Funding

This work was supported by 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No: ZYJC21044).