OC-096 TH17 cells are increased in<i>Helicobacter pylori</i>infection and may be associated with peptic ulcer disease
Authors: E Staples, R J M Ingram, K Hussain, D P Letley, J C Atherton, K Robinson
Journal: Gut (2012)

<h3>Introduction</h3> <i>Helicobacter pylori</i> (<i>Hp</i>) persistently colonises the stomachs of half the world9s population. The majority of hosts remain asymptomatic but 10%–15% will develop peptic ulcer disease (PUD) or gastric cancer. Disease is associated with an IFNγ-producing T-helper 1 (Th1) response. Pro-inflammatory IL-17-producing T-helper 17 (Th17) cells, which express the transcription factor RORC2, are also likely to be involved. The murine Th17 response to <i>Hp</i> has been characterised but the role of human Th17 responses remains unclear. <h3>Aim</h3> To assess the importance of Th17 cells in <i>Hp</i>+ patients. We quantified Th17 cells in the human gastric mucosa, compared <i>IL17</i>, <i>RORC2</i> and <i>IFNG</i> transcription, and investigated correlations with PUD. <h3>Methods</h3> Gastric biopsies were donated by patients undergoing routine upper GI endoscopy at Queen9s Medical Centre in Nottingham with informed consent and ethical approval. Patient characteristics: 17 with <i>Hp</i>−associated PUD, 28 with <i>Hp</i>-associated gastritis and 17 uninfected (<i>Hp</i>−). Antral <i>IL17</i> and <i>RORC2</i> mRNA levels (all patient biopsies) and <i>IFNG</i> transcription (26 <i>Hp</i>+ and 9 <i>Hp</i>− biopsies) and were quantified by real time PCR (RT-qPCR) relative to a comparator prepared from a further 14 uninfected biopsies. Frequencies of IL-17-secreting CD4<sup>+</sup> and CD8<sup>+</sup> T-cells were assessed by flow cytometry in gastric biopsies donated by 12 <i>Hp</i>+ and 11 <i>Hp</i>− patients. <h3>Analysis</h3> Comparisons between <i>Hp</i>+ and <i>Hp</i>− groups and patients with and without PUD used Mann–Whitney tests. Levels of mRNA expression for paired biopsies were compared with Wilcoxon signed rank tests. Spearman9s rank correlation was used to analyse relationships. <h3>Results</h3> Increased frequencies of CD4<sup>+</sup>IL-17<sup>+</sup> Th17 (3.0-fold, p=0.001) and CD8<sup>+</sup>IL-17<sup>+</sup> (Tc17) cells (3.3-fold, p=0.01) were present in <i>Hp</i>+ samples. RT-qPCR showed that infected patients have increased mucosal <i>IL17</i> (45.0-fold, p&lt;0.0001) and <i>IFNG</i> expression (3.4-fold, p=0.006) and showed for the first time that <i>RORC2</i> expression was also higher (2.6-fold, p&lt;0.0001). There was a trend towards a correlation between <i>IL17</i> and <i>IFNG</i> expression (r=0.39, p=0.051) and relative <i>IL17</i> expression was 3.1-fold higher than <i>IFNG</i> (p=0.0006). Relative <i>RORC2</i> gene expression was also 35% higher in tissue from <i>Hp</i>+ patients with PUD than in those with gastritis alone but this did not reach statistical significance (p=0.11). <h3>Conclusion</h3> The <i>Hp</i>-infected human stomach has increased frequencies of Th17 and Tc17 cells, and increased expression of <i>IL17</i>, <i>RORC2</i> and <i>IFNG</i>. <i>IL17</i> expression was significantly higher than <i>IFNG</i> expression, though the sources of <i>IL17</i> have yet to be fully characterised. There was a trend for increased <i>RORC2</i> expression in PUD. Our data suggest that Th17 cell responses may influence the clinical outcome of <i>Hp</i> infection in patients. <h3>Competing interests</h3> None declared.