Cytokine BAFF released by Helicobacter pylori-infected macrophages triggers the Th17 response in human chronic gastritis

BAFF is a crucial cytokine that affects the activity of both innate and adaptive immune cells. It promotes the expansion of Th17 cells in autoimmune disorders. With this study, we investigated the BAFF/Th17 responses in Helicobacter pylori-induced gastritis in humans. Our results show that the mucos...

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Vydáno v:The Journal of immunology (1950) Ročník 193; číslo 11; s. 5584
Hlavní autoři: Munari, Fabio, Fassan, Matteo, Capitani, Nagaja, Codolo, Gaia, Vila-Caballer, Marian, Pizzi, Marco, Rugge, Massimo, Della Bella, Chiara, Troilo, Arianna, D'Elios, Sofia, Baldari, Cosima T, D'Elios, Mario M, de Bernard, Marina
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.12.2014
Témata:
Adaptive Immunity
B-Cell Activating Factor - metabolism
Cell Differentiation
Cells, Cultured
Chronic Disease
Gastritis - etiology
Gastritis - immunology
Helicobacter Infections - complications
Helicobacter Infections - immunology
Helicobacter pylori - immunology
Humans
Immunity, Innate
Interleukin-17 - metabolism
Macrophages - immunology
Macrophages - microbiology
Mucous Membrane - immunology
Mucous Membrane - microbiology
Reactive Oxygen Species - metabolism
Th17 Cells - immunology
ISSN:1550-6606, 1550-6606
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Shrnutí:BAFF is a crucial cytokine that affects the activity of both innate and adaptive immune cells. It promotes the expansion of Th17 cells in autoimmune disorders. With this study, we investigated the BAFF/Th17 responses in Helicobacter pylori-induced gastritis in humans. Our results show that the mucosa from Helicobacter(+) patients with chronic gastritis is enriched in IL-17 and BAFF, whereas the two cytokines are weakly expressed in Helicobacter(-) patients with chronic gastritis; moreover, the expression of both BAFF and IL-17 decreases after bacteria eradication. We demonstrate that BAFF accumulates in macrophages in vivo and that it is produced by monocyte-derived macrophages in vitro, after Helicobacter stimulation. Application of BAFF on monocytes triggers the accumulation of reactive oxygen species that are crucial for the release of pro-Th17 cytokines, such as IL-23, IL-1β, and TGF-β. Moreover, BAFF directly promotes the differentiation of Th17 cells. In conclusion, our results support the notion that an axis BAFF/Th17 exists in chronic gastritis of Helicobacter(+) patients and that its presence strictly depends on the bacterium. Moreover, we demonstrated that BAFF is able to drive Th17 responses both indirectly, by creating a pro-Th17 cytokine milieu through the involvement of innate immune cells, and directly, via the differentiation of T cells toward the specific profile. The results obtained in this study are of great interest for Helicobacter-related diseases and the development of novel therapeutic strategies based on the inhibition of the BAFF/IL-17 response.
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ISSN:1550-6606
1550-6606
DOI:10.4049/jimmunol.1302865