title: Cytokine BAFF released by Helicobacter pylori-infected macrophages triggers the Th17 response in human chronic gastritis.
abstract: 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.
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy;
authors.forename: Fabio
authors.initials: F
authors.lastname: Munari
authors.affiliation: Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University of Verona, 37134 Verona, Italy;
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; Department of Life Sciences, University of Siena, 53100 Siena, Italy; and.
authors.forename: Nagaja
authors.initials: N
authors.lastname: Capitani
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy;
authors.forename: Gaia
authors.initials: G
authors.lastname: Codolo
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy;
authors.forename: Marian
authors.initials: M
authors.lastname: Vila-Caballer
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padua, 35121 Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.affiliation: Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padua, 35121 Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
authors.forename: Chiara
authors.initials: C
authors.lastname: Della Bella
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
authors.forename: Arianna
authors.initials: A
authors.lastname: Troilo
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
authors.forename: Sofia
authors.initials: S
authors.lastname: D'Elios
authors.affiliation: Department of Life Sciences, University of Siena, 53100 Siena, Italy; and.
authors.forename: Cosima T
authors.initials: CT
authors.lastname: Baldari
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; marina.debernard@unipd.it delios@unifi.it.
authors.forename: Mario M
authors.initials: MM
authors.lastname: D'Elios
authors.affiliation: Department of Biology, University of Padua, 35121 Padua, Italy; marina.debernard@unipd.it delios@unifi.it.
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D056704:Adaptive Immunity; D053264:B-Cell Activating Factor / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002908:Chronic Disease; D005756:Gastritis / Q000209:etiology / Q000276:immunology*; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D020381:Interleukin-17; D017382:Reactive Oxygen Species; C505719:TNFSF13B protein, human