Helicobacter pylori secreted peptidyl prolyl cis, trans-isomerase drives Th17 inflammation in gastric adenocarcinoma.
Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer.
Department of Internal Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.
Amedeo
A
Amedei
Fabio
F
Munari
Chiara Della
CD
Bella
Elena
E
Niccolai
Marisa
M
Benagiano
Lapo
L
Bencini
Fabio
F
Cianchi
Marco
M
Farsi
Giacomo
G
Emmi
Giuseppe
G
Zanotti
Marina
M
de Bernard
Manikuntala
M
Kundu
Mario Milco
MM
D'Elios
D000230:Adenocarcinoma / Q000276:immunology*; D005260:Female; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis* / Q000502:physiology*; D013274:Stomach Neoplasms / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019696:Peptidylprolyl Isomerase