Abstract
Abnormalities of forkhead box P3 (FOXP3) are implicated in various autoimmune diseases. This study is aimed at investigating the association of ulcerative colitis (UC) with FOXP3 polymorphisms and its colonic expression in Chinese patients. Polymorphisms of rs3761548, rs2232365, rs2294021, and rs3761547 were examined in 472 UC patients and 525 healthy controls using the SNaPshot method. The colonic expression of FOXP3 mRNA and protein was assayed in inflammatory mucosa of 34 UC patients and normal mucosa of 36 patients with benign sigmoid polyps (normal controls) using real-time quantitative polymerase chain reaction and immunohistochemical analysis. All data were handled separately for females and males. As a result, the carrier frequencies with at least one variant allele of rs3761548, rs2232365, and rs229402 increased in female and male UC patients compared with healthy controls. Significant differences in these carrier frequencies were also observed between patients with mild and moderate UC and patients with severe UC. The expression of FOXP3 was higher in UC patients (both males and females), especially those with severe UC, than in normal controls. The expression of FOXP3 was downregulated in UC patients having at least one variant allele compared with UC patients having no variant allele of rs3761548, rs2232365, and rs2294021. Male gender (β = −0.341), rs2294021 variation (β = −0.503), and severe UC (β = 0.361) were independently related to the mRNA expression of FOXP3 in UC patients. Together, our findings indicated that FOXP3 (rs3761548, rs2232365, and rs2294021) variations increased the risk of UC and were associated with the lower colonic expression of FOXP3 in UC patients.
Highlights
Regulatory T cells (Tregs), especially those that coexpress CD4 and CD25, are crucial in the suppression of immune response and orchestration of immune tolerance
When male patients with ulcerative colitis (UC) were compared with male healthy controls, the same results were obtained for variant alleles of the three single-nucleotide polymorphisms (SNPs) (Table 2)
Rs3 761548 is located on forkhead box P3 (FOXP3) at position -3279, while rs 2232365 is positioned at -924
Summary
Regulatory T cells (Tregs), especially those that coexpress CD4 and CD25, are crucial in the suppression of immune response and orchestration of immune tolerance. The numerical or functional abnormality of Tregs is further confirmed to cause a breach in self-tolerance and is closely involved in a range of immune-related diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD). Revealed that the number of Tregs was higher in the inflamed mucosa of patients with IBD than in healthy individuals, but significantly lower compared with other inflammatory conditions, such as diverticulitis [5]. Antitumor necrosis factor treatment, a well-described and effective approach to treating IBD, has been demonstrated to facilitate the increase in the number of Tregs in the circulation and colonic mucosa of patients with IBD [6, 7], highlighting that dysregulation of Tregs may have an impact on the progression of IBD
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
