Dataset Information

Decreased Frequency of Intestinal Regulatory CD5+ B Cells in Colonic Inflammation.

ABSTRACT: BACKGROUND:CD5+ B cells are a type of regulatory immune cells, though the involvement of this B cell subset in intestinal inflammation and immune regulation is not fully understood. METHODS:We examined the distribution of CD5+ B cells in various mouse organs. Expression levels of CD11b, IgM, and toll-like receptor (TLR)-4 and -9 in B cells were evaluated. In vitro, TLR-stimulated IL-10 production by colonic lamina propria (LP) CD5+ and CD5- B cells was measured. In vivo, mice with acute or chronic dextran sulfate sodium (DSS)-induced colonic injury were examined, and the frequency of colonic LP CD5+ B cells in those was assessed by flow cytometry. RESULTS:The expression level of TLR9 was higher in colonic LP CD5+ B cells as compared to CD5- B cells. Colonic LP CD5+ B cells produced greater amounts of IL-10 following stimulation with TLR ligands, especially TLR9, as compared with the LP CD5- B cells. Acute intestinal inflammation transiently decreased the frequency of colonic LP CD5+ B cells, while chronic inflammation induced a persistent decrease in colonic LP CD5+ B cells and led to a CD5- B cell-dominant condition. CONCLUSION:A persistent altered mucosal B cell population caused by chronic gut inflammation may be involved in the pathogenesis of inflammatory bowel diseases.

SUBMITTER: Mishima Y

PROVIDER: S-EPMC4705109 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Decreased Frequency of Intestinal Regulatory CD5+ B Cells in Colonic Inflammation.

Mishima Yoshiyuki Y Ishihara Shunji S Oka Akihiko A Fukuba Nobuhiko N Oshima Naoki N Sonoyama Hiroki H Yamashita Noritsugu N Tada Yasumasa Y Kusunoki Ryusaku R Moriyama Ichiro I Yuki Takafumi T Kawashima Kousaku K Kinoshita Yoshikazu Y

PloS one 20160104 1

<h4>Background</h4>CD5+ B cells are a type of regulatory immune cells, though the involvement of this B cell subset in intestinal inflammation and immune regulation is not fully understood.<h4>Methods</h4>We examined the distribution of CD5+ B cells in various mouse organs. Expression levels of CD11b, IgM, and toll-like receptor (TLR)-4 and -9 in B cells were evaluated. In vitro, TLR-stimulated IL-10 production by colonic lamina propria (LP) CD5+ and CD5- B cells was measured. In vivo, mice with ...[more]

PMID: 26727001

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Project description:Background & aimsInnate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation.MethodsILCs were isolated from colons of Tbx21(-/-) × Rag2(-/-) mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota.ResultsIL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner.ConclusionsIL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells.

Dataset Information

Decreased Frequency of Intestinal Regulatory CD5+ B Cells in Colonic Inflammation.

Publications

Decreased Frequency of Intestinal Regulatory CD5+ B Cells in Colonic Inflammation.

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