Helicobacter pylori promotes the production of thymic stromal lymphopoietin by gastric epithelial cells and induces dendritic cell-mediated inflammatory Th2 responses.
Helicobacter pylori colonizes the stomach and induces strong, specific local and systemic humoral and cell-mediated immunity, resulting in the development of chronic gastritis in humans. Although H. pylori-induced chronic atrophic gastritis is characterized by marked infiltration of T helper type 1 (Th1) cytokine-producing CD4(+) T cells, almost all of the inflamed gastric mucosae also contain focal lymphoid aggregates with germinal centers. In addition, typical H. pylori-induced chronic gastritis in children, called follicular gastritis, is characterized by B-cell follicle formation in the gastric mucosa. The aim of this study was to examine whether thymic stromal lymphopoietin (TSLP), an epithelial-cell-derived cytokine inducing a dendritic cell (DC)-mediated inflammatory Th2 response, is involved in Th2 responses triggering B-cell activation in H. pylori-induced gastritis. Here, we show that H. pylori triggered human gastric epithelial cells to produce TSLP, together with the DC-attracting chemokine MIP-3alpha and the B-cell-activating factor BAFF. After DCs were incubated with supernatants from H. pylori-infected epithelial cells, the conditioned cells expressed high levels of costimulatory molecules, such as CD80, and triggered naïve CD4(+) T cells to produce high levels of the Th2 cytokines interleukin-4 and interleukin-13 and of the inflammatory cytokines tumor necrosis factor alpha and gamma interferon. In contrast, after incubation of the supernatants with the neutralizing antibodies to TSLP, the conditioned DCs did not prime T cells to produce high levels of Th2 cytokines. These results, together with the finding that TSLP was expressed by the epithelial cells of human follicular gastritis, suggest that H. pylori can directly trigger epithelial cells to produce TSLP. It also suggests that TSLP-mediated DC activation may be involved in Th2 responses triggering B-cell activation in H. pylori-induced gastritis.
Department of Gastroenterology and Hepatology, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Masahiro
M
Kido
Junya
J
Tanaka
Nobuhiro
N
Aoki
Satoru
S
Iwamoto
Hisayo
H
Nishiura
Tsutomu
T
Chiba
Norihiko
N
Watanabe
D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D044922:Helicobacter felis; D016480:Helicobacter pylori; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D013274:Stomach Neoplasms; D018418:Th2 Cells / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
D053264:B-Cell Activating Factor; D018122:B7-1 Antigen; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D016207:Cytokines; C505719:TNFSF13B protein, human; D000094632:Thymic Stromal Lymphopoietin