TY - JOUR
T1 - Role of the IL-23-T-bet/GATA3 Axis for the Pathogenesis of Ulcerative Colitis
AU - Ogino, Haruei
AU - Fukaura, Keita
AU - Iboshi, Yoichiro
AU - Nagamatsu, Yousuke
AU - Okuno, Hiroaki
AU - Nishioka, Kei
AU - Nishihara, Yuichiro
AU - Tanaka, Yoshimasa
AU - Chinen, Takatoshi
AU - Ihara, Eikich
AU - Ogawa, Yoshihiro
N1 - Funding Information:
We sincerely thank the staff of the endoscopy unit at Kyushu Medical Center, Kitakyushu Municipal Medical Center, and Harasanshin Hospital for their valuable assistance in conducting this study. We appreciate the technical assistance received from The Research Support Center, Research Center for Human Disease Modeling, and Kyushu University Graduate School of Medical Sciences.
Funding Information:
This study was supported in part by the Japan Society for the Promotion of Science KAKENHI (20K08389). Acknowledgments
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
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U2 - 10.1007/s10753-020-01358-y
DO - 10.1007/s10753-020-01358-y
M3 - Article
C2 - 33040251
AN - SCOPUS:85092311229
VL - 44
SP - 592
EP - 603
JO - Inflammation
JF - Inflammation
SN - 0360-3997
IS - 2
ER -