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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

  • Original Article—Alimentary Tract
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An Erratum to this article was published on 27 June 2016

Abstract

Background

T helper (Th) and regulatory T (Treg) 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 Th/Treg-related genes.

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Acknowledgments

We thank Naoko Yamamoto for advice on performing the experiments.

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Authors and Affiliations

  1. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan

    Yoichiro Iboshi, Kazuhiko Nakamura, Keita Fukaura, Tsutomu Iwasa & Eikichi Ihara

  2. Department of Gastroenterology, Kyushu Medical Center, Clinical Research Center, National Hospital Organization, Fukuoka, Japan

    Yoichiro Iboshi, Yorinobu Sumida, Naohiko Harada & Makoto Nakamuta

  3. Department of Gastroenterology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Haruei Ogino & Hirotada Akiho

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  1. Yoichiro Iboshi
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Correspondence to Kazuhiko Nakamura.

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The authors declare that they have no conflict of interest.

Funding

This work was supported in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant Number 20590743).

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An erratum to this article is available at http://dx.doi.org/10.1007/s00535-016-1231-z.

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Iboshi, Y., Nakamura, K., Fukaura, K. et al. Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis. J Gastroenterol 52, 315–326 (2017). https://doi.org/10.1007/s00535-016-1221-1

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