Role of the IL-23-T-bet/GATA3 Axis for the Pathogenesis of Ulcerative Colitis

• Published in: Inflammation Vol. 44; no. 2; pp. 592 - 603
• Main Authors: Ogino, Haruei, Fukaura, Keita, Iboshi, Yoichiro, Nagamatsu, Yousuke, Okuno, Hiroaki, Nishioka, Kei, Nishihara, Yuichiro, Tanaka, Yoshimasa, Chinen, Takatoshi, Ihara, Eikich, Ogawa, Yoshihiro
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2021; Springer Nature B.V
• Subjects: Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Biopsy; Correlation analysis; Cytokines; GATA-3 protein; Helper cells; Immune response; Immunology; Inflammation; Inflammatory bowel disease; Interleukin 12; Interleukin 23; Internal Medicine; Lymphocytes T; Mucosa; Original Article; Pathogenesis; Pathology; Patients; Pharmacology/Toxicology; Polymerase chain reaction; Remission; Rheumatology; Transcription factors; Ulcerative colitis; GATA3; IL-23; T-bet; UC
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-020-01358-y

Ulcerative colitis (UC) has been considered a Th2- and Th17-related disease. However, anti-IL-12/23 p40 antibody, which blocks Th1 and Th17 cell induction and maintenance, has shown efficacy in treating UC, suggesting that UC might not be a prototypical Th2 and Th17 cell-mediated autoimmune disease. To verify how the immune responses in UC patients interact with each other, we analyzed the cytokine expression and transcription factors involved in the Th1, Th2, and Th17 responses. The mucosal expression of 19 cytokines and transcription factors related to Th1, Th2, and Th17 cells, as well as Tregs, were measured by quantitative polymerase chain reaction using endoscopic biopsy specimens from inflamed colons of UC patients. A correlation analysis between the cytokines and transcription factors was conducted. The characteristic cytokine profile in UC patients has two immune response clusters: Th17-related responses and Th1-/Th2-related responses. IL-23 showed a weaker association with Th17 cell-related cytokines and transcription factor RORC and a much stronger correlation with T-bet and GATA3. In the high-IL-23-expression group, the rate of chronic continuous type was higher and the remission rate lower than in the low-IL-23-expression group. IL-23 may be a very important cytokine for evaluating the UC disease condition, as the expression of IL-23 is associated with certain clinical characteristics of UC patients. A unique association between IL-23 and T-bet/GATA3 might play a key role in the pathogenesis of UC.