期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.952674
关键词
T cells; Th17; gastric autoantigen; gastric autoimmunity; gastric cancer; H+; K+-ATPase; serum IL-17; gastric mucosal immunity
类别
This study investigated the gastric H+/K+-ATPase-specific Th17 responses and serum IL-17 cytokine subfamily in AIG patients, showing that gastric LPMCs from AIG patients are activated by H+/K+-ATPase and produce high levels of IL-17A and IL-17F, while serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients.
Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+/K+-adenosine triphosphatase (H+/K+-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+/K+-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+/K+-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+/K+-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 +/- 410.02 pg/ml, 394.0 +/- 378.03 pg/ml, 300.46 +/- 303.45 pg/ml, 34.92 +/- 32.56 pg/ml, respectively) than those in HCs (222.99 +/- 361.24 pg/ml, 217.49 +/- 312.1 pg/ml, 147.43 +/- 259.17 pg/ml, 8.69 +/- 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 +/- 107.49 pg/ml, 74.26 +/- 178.50 pg/ml, 96.86 +/- 177.46 pg/ml, 10.64 +/- 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+/K+-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.
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