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13.05.2016 | Original Article—Alimentary Tract

Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis

verfasst von: Yoichiro Iboshi, Kazuhiko Nakamura, Keita Fukaura, Tsutomu Iwasa, Haruei Ogino, Yorinobu Sumida, Eikichi Ihara, Hirotada Akiho, Naohiko Harada, Makoto Nakamuta

Erschienen in: Journal of Gastroenterology | Ausgabe 3/2017

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Abstract

Background

T helper (T_h) and regulatory T (T_reg) cell-related cytokines are implicated in inflammatory bowel diseases, including ulcerative colitis (UC). While these cytokines are generally upregulated in inflamed mucosae, the key cytokine profile explaining disease severity has not been determined.

Methods

The Rachmilewitz endoscopic index (REI) was assessed in 61 UC patients undergoing colonoscopy. Biopsies obtained from inflamed (REI 3–12) and noninflamed (REI 0–2) areas were analyzed by quantitative PCR for expression of mRNAs encoding cytokines and transcription factors related to Th1 (TNF-α, IFN-γ, IL-12p35, IL-12p40, and T-bet), Th2 (IL-4, IL-13, IL-33, and GATA3), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23p19, IL-6, and RORC), Th9 (IL-9, IRF4, and PU.1), and Treg (TGF-β and Foxp3). Expression patterns associated with higher REI were determined by univariate and multivariate analyses.

Results

Despite general upregulation, none of these mRNAs showed univariate correlation with REI in inflamed samples. Multiple regression analysis, however, found that joint expression of IL-17A, IL-17F, IL-21, RORC, and TGF-β was significantly predictive of REI (P < 0.0002, R² = 0.380), with major individual contributions by IL-17A (P < 0.0001) and IL-17F (P < 0.0001), which were associated with increased and decreased REI, respectively. Partial correlation analysis, validating this model, indicated differences between IL-17A and IL-17F in correlating with other targets. The IL-17A/IL-17F ratio showed a significant correlation with REI (r = 0.5124, P < 0.0001), whereas no other mRNAs were essentially predictive of REI.

Conclusions

Mucosal IL-17A/IL-17F ratio significantly correlates with endoscopic score in UC patients, accompanied by their disparate interactions with other T_h/T_reg-related genes.

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Titel: Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis
verfasst von: Yoichiro Iboshi
Kazuhiko Nakamura
Keita Fukaura
Tsutomu Iwasa
Haruei Ogino
Yorinobu Sumida
Eikichi Ihara
Hirotada Akiho
Naohiko Harada
Makoto Nakamuta
Publikationsdatum: 13.05.2016
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 3/2017
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-016-1221-1

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Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis

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