Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2016; 22(42): 9356-9367
Published online Nov 14, 2016. doi: 10.3748/wjg.v22.i42.9356
Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice
Ya-Hui Ma, Jie Zhang, Xue Chen, You-Fu Xie, Yan-Hua Pang, Xin-Juan Liu
Ya-Hui Ma, Jie Zhang, Xue Chen, Department of Gastroenterology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
You-Fu Xie, Yan-Hua Pang, Xin-Juan Liu, Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Author contributions: Ma YH and Zhang J contributed equally to this work; Ma YH, Zhang J performed the research and wrote the manuscript; Chen X, Xie YF, Pang YH analyzed the data; Liu XJ designed the research; all authors have read and approved the final version to be published.
Supported by the National Natural Science Foundation of China, No. 81300294; and State Scholarship Fund of China, No. 201509110033.
Institutional review board statement: The study was reviewed and Supported by Beijing Chaoyang Hospital, Capital Medical University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Beijing Chaoyang Hospital, Capital Medical University.
Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of the manuscript.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xin-Juan Liu, PhD, MD, Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Chaoyang District, Beijing 100020, China. lxjw2012@126.com
Telephone: +86-10-85231714
Received: May 10, 2016
Peer-review started: May 11, 2016
First decision: July 13, 2016
Revised: August 5, 2016
Accepted: August 19, 2016
Article in press: August 19, 2016
Published online: November 14, 2016
Processing time: 185 Days and 20.2 Hours
Abstract
AIM

To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.

METHODS

Treg cells, Treg cell subsets, Th17 cells, and CD4+CD25+FoxP3+IL-17+ cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array.

RESULTS

In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased (P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4+CD45RA+FoxP3low) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4+CD45RA-FoxP3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4+CD45RA-FoxP3low) and CD4+CD25+FoxP3+IL-17A+ cells was increased. FoxP3 mRNA levels in CD4+CD45RA-FoxP3low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP3high, and CD4+CD45RA-FoxP3low cells was higher in LPC relative to other tissues.

CONCLUSION

Increased numbers of CD4+CD45RA-FoxP3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.

Keywords: Ulcerative colitis; Regulatory T cells; Treg cells subsets; T helper 17 cells

Core tip: The exact etiology and pathology of ulcerative colitis (UC) remains unknown. Here we investigated the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. In this study we found that increased numbers of CD4+CD45RA-FoxP3low cells may cause an imbalance between Treg and Th17 cells, which was mainly localized to the lamina propria of colon rather than secondary lymphoid tissues. Based on our findings, lamina propria-resident Treg cells appear to play important roles in shaping local peripheral tolerance and maintaining intestinal homeostasis, and an imbalance of Treg and Th17 cells in the lamina propria of the colon is critical for UC pathogenesis.