Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2019; 25(20): 2473-2488
Published online May 28, 2019. doi: 10.3748/wjg.v25.i20.2473
Interleukin-22 receptor 1 is expressed in multinucleated giant cells: A study on intestinal tuberculosis and Crohn's disease
Zi-Qi Yu, Wen-Fei Wang, You-Chao Dai, Xin-Chun Chen, Jian-Yong Chen
Zi-Qi Yu, Jian-Yong Chen, Department of Gastroenterology and Hepatology, Jiangxi Provincial People’s Hospital, Nanchang 330006, Jiangxi Province, China
Zi-Qi Yu, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
Wen-Fei Wang, You-Chao Dai, Xin-Chun Chen, Department of Microbiology and Immunology, Shenzhen University Health Science Center, Shenzhen 518000, Guangdong Province, China
Wen-Fei Wang, Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University, Jena 07743, Germany
Author contributions: Chen JY, Chen XC, Wang WF, and Yu ZQ designed the research; Yu ZQ, Wang WF, and Dai YC performed the research; Yu ZQ and Wang WF analyzed the data; Yu ZQ wrote the paper.
Supported by: Key R&D Plan of Science and Technology Department of Jiangxi Province, No. 20171BBG70087.
Institutional review board statement: The study was reviewed and approved by the Jiangxi Provincial People's Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
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:
Corresponding author: Jian-Yong Chen, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology and Hepatology, Jiangxi Provincial People’s Hospital, 92 Aiguo Road, Donghu district, Nanchang 330006, Jiangxi Province, China.
Telephone: +86-180-70088908 Fax: +86-791-86895621
Received: February 12, 2019
Peer-review started: February 15, 2019
First decision: April 4, 2019
Revised: April 20, 2019
Accepted: April 29, 2019
Article in press: April 29, 2019
Published online: May 28, 2019

It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells.


To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease.


We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry.


The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01).


High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

Keywords: Crohn’s disease, Intestinal tuberculosis, Single-nucleotide polymorphism, Interleukin-22, Interleukin-22 receptor 1, Multinucleated giant cells

Core tip: The interleukin-22 (IL22) gene promoter SNP rs2227473 G allele is a risk factor for intestinal tuberculosis. High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is not only highly expressed in epithelial cells but also, unexpectedly, expressed in Langhans giant cells, contradicting the previous view that IL-22R1 is expressed only in non-haematopoietic cells. Importantly, these data provide a premise for elucidating the role of the IL-22/IL-22R1 system in the crosstalk between innate and adaptive immunity under conditions of chronic inflammation. Researchers should pay more attention to the immunological side effects of therapeutic modulation of the IL-22/IL-22R1 axis.