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Berberine improved experimental chronic colitis by regulating interferon-?- and IL-17A-producing lamina propria CD4⁺ T cells through AMPK activation.

ABSTRACT: The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4⁺T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4⁺ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4⁺CD45RB^high T cells. BBR suppressed the frequency of IFN-?- and Il-17A-producing LP CD4⁺ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4⁺ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4⁺ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

SUBMITTER: Takahara M

PROVIDER: S-EPMC6695484 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation.

Takahara Masahiro M Takaki Akinobu A Hiraoka Sakiko S Adachi Takuya T Shimomura Yasuyuki Y Matsushita Hiroshi H Nguyen Tien Thi Thuy TTT Koike Kazuko K Ikeda Airi A Takashima Shiho S Yamasaki Yasushi Y Inokuchi Toshihiro T Kinugasa Hideaki H Sugihara Yusaku Y Harada Keita K Eikawa Shingo S Morita Hidetoshi H Udono Heiichiro H Okada Hiroyuki H

Scientific reports 20190815 1

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells ...[more]

PMID: 31417110

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Project description:BackgroundSalmonella enterica serovar Typhi (S. Typhi) is a highly invasive bacterium that infects the human intestinal mucosa and causes ~ 11.9-20.6 million infections and ~ 130,000-223,000 deaths annually worldwide. Oral typhoid vaccine Ty21a confers a moderate level of long-lived protection (5-7 years) in the field. New and improved vaccines against enteric pathogens are needed but their development is hindered by a lack of the immunological correlates of protection especially at the site of infection. Tissue resident memory T (TRM) cells provide immediate adaptive effector immune responsiveness at the infection site. However, the mechanism(s) by which S. Typhi induces TRM in the intestinal mucosa are unknown. Here, we focus on the induction of S. Typhi-specific CD4+TRM subsets by Ty21a in the human terminal ileum lamina propria and epithelial compartments.MethodsTerminal ileum biopsies were obtained from consenting volunteers undergoing routine colonoscopy who were either immunized orally with 4 doses of Ty21a or not. Isolated lamina propria mononuclear cells (LPMC) and intraepithelial lymphocytes (IEL) CD4+TRM immune responses were determined using either S. Typhi-infected or non-infected autologous EBV-B cell lines as stimulator cells. T-CMI was assessed by the production of 4 cytokines [interferon (IFN)γ, interleukin (IL)-2, IL-17A and tumor necrosis factor (TNF)α] in 36 volunteers (18 vaccinees and 18 controls volunteers).ResultsAlthough the frequencies of LPMC CD103+ CD4+TRM were significant decreased, both CD103+ and CD103- CD4+TRM subsets spontaneously produced significantly higher levels of cytokines (IFNγ and IL-17A) following Ty21a-immunization. Importantly, we observed significant increases in S. Typhi-specific LPMC CD103+ CD4+TRM (IFNγ and IL-17A) and CD103- CD4+TRM (IL-2 and IL-17A) responses following Ty21a-immunization. Further, differences in S. Typhi-specific responses between these two CD4+TRM subsets were observed following multifunctional analysis. In addition, we determined the effect of Ty21a-immunization on IEL and observed significant changes in the frequencies of IEL CD103+ (decrease) and CD103- CD4+TRM (increase) following immunization. Finally, we observed that IEL CD103- CD4+TRM, but not CD103+ CD4+TRM, produced increased cytokines (IFNγ, TNFα and IL-17A) to S. Typhi-specific stimulation following Ty21a-immunization.ConclusionsOral Ty21a-immunization elicits distinct compartment specific immune responses in CD4+TRM (CD103+ and CD103-) subsets. This study provides novel insights in the generation of local vaccine-specific responses. Trial registration This study was approved by the Institutional Review Board and registered on ClinicalTrials.gov (identifier NCT03970304, Registered 29 May 2019-Retrospectively registered, http://www.ClinicalTrials.gov/NCT03970304).

Dataset Information

Berberine improved experimental chronic colitis by regulating interferon-?- and IL-17A-producing lamina propria CD4⁺ T cells through AMPK activation.

Publications

Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4<sup>+</sup> T cells through AMPK activation.

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Dataset Information

Berberine improved experimental chronic colitis by regulating interferon-?- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation.

Publications

Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4<sup>+</sup> T cells through AMPK activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Berberine improved experimental chronic colitis by regulating interferon-?- and IL-17A-producing lamina propria CD4⁺ T cells through AMPK activation.