Recruitment of CCR6⁺Foxp3⁺ regulatory gastric infiltrating lymphocytes in <i>Helicobacter pylori</i> gastritis

<jats:title>Abstract</jats:title><jats:p><jats:italic>Helicobacter pylori</jats:italic> (<jats:italic>H. pylori</jats:italic>) infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, and gastric cancer. Increased T‐cell infiltration is found at sites of <jats:italic>H. pylori</jats:italic> infection. The CCR6<jats:sup>+</jats:sup> subset of CD4<jats:sup>+</jats:sup> regulatory T cells (Tregs), a newly characterized subset of Tregs, has been reported to contribute to local immune inhibition. However, whether CCR6<jats:sup>+</jats:sup> Tregs are present in <jats:italic>H. pylori</jats:italic> gastritis, and what their relationship is to disease prognosis, remains to be elucidated. In this study, gastric infiltrating lymphocytes were isolated from endoscopic biopsy specimens of <jats:italic>H. pylori</jats:italic> gastritis patients and analyzed. We found that in gastric infiltrating lymphocytes, CCR6<jats:sup>+ </jats:sup>CD4<jats:sup>+ </jats:sup>CD25<jats:sup>high</jats:sup> Tregs, which express high levels of CD45RO, are positively associated with more severe inflammation in gastric mucosa during <jats:italic>H. pylori</jats:italic> infection. Furthermore, the frequency of CCR6<jats:sup>+</jats:sup> Tregs in gastric infiltrating lymphocytes, but not CCR6<jats:sup>−</jats:sup> Tregs, is significantly increased in inflamed gastric tissues, which is inversely correlated with significantly lower expression of IFN‐γ<jats:sup>+ </jats:sup>CD8<jats:sup>+</jats:sup> T cells. We also found that the frequency of CCR6<jats:sup>+</jats:sup> Tregs is positively correlated with the frequency of CD4<jats:sup>+ </jats:sup>IFN‐γ<jats:sup>+</jats:sup> T cells. In addition, the frequency of CCR6<jats:sup>+</jats:sup> Tregs, but not that of CCR6<jats:sup>−</jats:sup> Tregs, is significantly correlated with increased inflammation in <jats:italic>H. pylori</jats:italic> gastritis. This study demonstrates that immunosuppression in <jats:italic>H. pylori</jats:italic> gastritis might be related to the activity of CCR6<jats:sup>+</jats:sup> Tregs, which could influence disease prognosis.</jats:p>