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Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells.

ABSTRACT: Rationale: Immune dysfunction is thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, the underlying mechanism requires further investigation. Vasoactive intestinal peptide (VIP) has immune regulatory functions, but its role in immune regulatory activities in the intestinal mucosa is not fully understood. This study aims to elucidate the role of VIP in the regulation of regulatory B cell (Breg) function in the intestine. Methods: Peripheral blood samples were collected from UC patients and healthy control (HC) subjects. Bregs were isolated from these samples and their immune regulatory function was analyzed. A murine colitis model was established to test the role of VIP in inhibiting inflammation in the intestine. Results: Serum IL-10 and VIP levels were lower in IgE+ (?0.35 IU/mL) UC patients than that in HC subjects. The immune suppressive function of Bregs isolated from IgE+ UC patients was impaired. IL-10 mRNA decayed spontaneously in Bregs, which was reversed by VIP added to the culture. Tristetraprolin (TTP) bound IL-10 mRNA to speed its decay, which was blocked by VIP in the culture. Administration of VIP efficiently inhibited experimental colitis. Conclusions: Insufficient VIP levels in the microenvironment speeds IL-10 mRNA decay to cause Breg dysfunction. Administration of VIP can inhibit experimental colitis, suggesting the translational potential of VIP in the treatment of IgE+ UC.

SUBMITTER: Sun X

PROVIDER: S-EPMC6568172 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells.

Sun Xiong X Guo Chuanyong C Zhao Fang F Zhu Jianhuan J Xu Yilu Y Liu Zhi-Qiang ZQ Yang Gui G Zhang Yuan-Yi YY Gu Xia X Xiao Liang L Liu Zhanju Z Yang Ping-Chang PC

Theranostics 20190413 10

<b>Rationale</b>: Immune dysfunction is thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, the underlying mechanism requires further investigation. Vasoactive intestinal peptide (VIP) has immune regulatory functions, but its role in immune regulatory activities in the intestinal mucosa is not fully understood. This study aims to elucidate the role of VIP in the regulation of regulatory B ...[more]

PMID: 31244924

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Project description:Background and aimsVasoactive intestinal peptide (VIP) is a neuropeptide involved in the regulation of feeding behavior and circadian rhythms, metabolism, and immunity. Previous studies revealed the homeostatic effects of VIP signaling on the gut microbiota. VIP-deficient mice demonstrate a gut microbiota dysbiosis characterized by reduced α-diversity and decreased relative abundance (RA) of Gram-positive Firmicutes. However, the mechanism by which VIP signaling affects changes in the microbiota is unknown.MethodsTo investigate the role of the 2 cognate G protein-coupled receptors for VIP (VPAC1 and VPAC2) in VIP-mediated homeostasis of the microbiota, fecal samples from VPAC1- and VPAC2-deficient, heterozygous, and wild-type littermate mice were assessed via targeted amplicon sequencing. Their microbiota profiles were additionally compared with microbiota from VIP-deficient, heterozygous, and wild-type littermates, where genotype-dependent changes in the composition and predicted function of each cohort were compared.ResultsWhile wild-type mice in each line differed in α-diversity and β-diversity, consistent changes in both metrics were observed in VIP-deficient and VPAC1-deficient mice. This includes a dramatic reduction in α-diversity, increased RA of Proteobacteria and Bacteroidetes, and decreased RA of Lachnospiraceae, Ruminococcaceae, Muribaculaceae, and Rikenellaceae. Specific amplicon sequence variants and predicted functions found to differ significantly based on VIP or VPAC1 genotype were concordant in their directions of change. Multiplatform predicted functional profiling suggested a defective VIP-VPAC1 axis was associated with reduced amino acid degradation along with reduced quinol and quinone biosynthesis. Furthermore, alterations in predicted functions include increased sugar degradation, nitrate reduction, and fatty acid biosynthetic pathways, among other changes.ConclusionWe conclude that VIP signaling through VPAC1 is critical for the maintenance of normal function of the gut microbiota.

Dataset Information

Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells.

Publications

Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells.

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