Decreased IL-17RB expression impairs CD11b+CD11c- myeloid cell accumulation in gastric mucosa and host defense during the early-phase of Helicobacter pylori infection.

Abstract:

:Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found that gastric IL-17RB mRNA and protein were decreased in gastric mucosa of both patients and mice infected with H. pylori. In vitro experiments show that IL-17RB expression was down regulated via PI3K/AKT pathway on gastric epithelial cells (GECs) stimulated with H. pylori in a cagA-involved manner, while in vivo studies showed that the effect was partially dependent on cagA expression. IL-17E was also decreased during the early-phase of H. pylori infection, and provision of exogenous IL-17E resulted in increased CD11b+CD11c- myeloid cells accumulation and decreased bacteria colonization within the gastric mucosa. In the early-phase of H. pylori infection, IL-17E-IL-17RB promoted gastric epithelial cell-derived CXCL1/2/5/6 to attract CD11b+CD11c- myeloid cells, and also contributed to host defense by promoting the production of antibacterial protein Reg3a. This study defines a negative regulatory network involving IL-17E, GECs, IL-17RB, CD11b+CD11c- myeloid cells, and Reg3a in the early-phase of H. pylori infection, which results in an impaired host defense within the gastric microenvironment, suggesting IL-17RB as a potential early intervening target in H. pylori infection.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Teng YS,Liu YG,Chen XH,Wang TT,Cheng P,Lv YP,Kong H,Mao FY,Hao CJ,Yang SM,Chen W,Zhang JY,Peng LS,Han B,Ma Q,Han J,Zou QM,Zhuang Y

doi

10.1038/s41419-019-1312-z

subject

Has Abstract

pub_date

2019-01-28 00:00:00

pages

79

issue

2

issn

2041-4889

pii

10.1038/s41419-019-1312-z

journal_volume

10

pub_type

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