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Berberine improves central memory formation of CD8⁺ T cells: Implications for design of natural product-based vaccines.

ABSTRACT: Berberine (BBR) as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities. However, it is unknown if BBR can be applied without abrogating the efforts of vaccination. Here we show that priming of CD8⁺ T cells in the presence of BBR lead to improved central memory formation (Tcm) with substantially reduced effector proliferation, primarily orchestrated through activation of AMPK and Stat5. Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naïve recipients. Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy, suggesting appreciable benefits from using BBR in vaccination. Thus, our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.

SUBMITTER: Li M

PROVIDER: S-EPMC10213802 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Berberine improves central memory formation of CD8<sup>+</sup> T cells: Implications for design of natural product-based vaccines.

Li Mingyan M Wang Yaling Y Zhang Lingzhi L Gao Changxing C Li Jing J JJ Jiang Jiandong J Zhu Qing Q

Acta pharmaceutica Sinica. B 20230228 5

Berberine (BBR) as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities. However, it is unknown if BBR can be applied without abrogating the efforts of vaccination. Here we show that priming of CD8<sup>+</sup> T cells in the presence of BBR lead to improved central memory formation (Tcm) with substantially reduced effector proliferation, primarily orchestrated through activation of AMPK and Sta ...[more]

PMID: 37250162

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Project description:Emerging evidence has linked the gut microbiota dysbiosis to transplant rejection while memory T-cells pose a threat to long-term transplant survival. However, it's unclear if the gut microbiome alters the formation and function of alloreactive memory T-cells. Here we studied the effects of berberine, a narrow-spectrum antibiotic that is barely absorbed when orally administered, on the gut microbiota, memory T-cells, and allograft survival. In this study, C57BL/6 mice transplanted with islets or a heart from BALB/c mice were treated orally with berberine. Allograft survival was observed, while spleen, and lymph node T-cells from recipient mice were analyzed using a flow cytometer. High-throughput sequencing and qPCR were performed to analyze the gut microbiota. CD8+ T-cells from recipients were cultured with the bacteria to determine potential T-cell memory cross-reactivity to a specific pathogen. We found that berberine suppressed islet allograft rejection, reduced effector CD8+CD44highCD62Llow and central memory CD8+CD44highCD62Lhigh T-cells (TCM), altered the gut microbiota composition and specifically lowered Bacillus cereus abundance. Further, berberine promoted long-term islet allograft survival induced by conventional costimulatory blockade and induced cardiac allograft tolerance as well. Re-colonization of B. cereus upregulated CD8+ TCM cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8+ T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8+ TCM through regulating the gut microbiota. We have provided the first evidence that donor-specific memory T-cell generation is linked to a specific microbe and uncovered a novel mechanism underlying the therapeutic effects of berberine. This study may be implicated for suppressing human transplant rejection since berberine is already used in clinic to treat intestinal infections.

Dataset Information

Berberine improves central memory formation of CD8⁺ T cells: Implications for design of natural product-based vaccines.

Publications

Berberine improves central memory formation of CD8<sup>+</sup> T cells: Implications for design of natural product-based vaccines.

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Dataset Information

Berberine improves central memory formation of CD8+ T cells: Implications for design of natural product-based vaccines.

Publications

Berberine improves central memory formation of CD8<sup>+</sup> T cells: Implications for design of natural product-based vaccines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Berberine improves central memory formation of CD8⁺ T cells: Implications for design of natural product-based vaccines.