Published online May 28, 2019. doi: 10.3748/wjg.v25.i20.2473
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.
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.