Dataset Information

IL-36β promotes anti-tumor effects in CD8⁺ T cells by downregulating micro-RNA let-7c-5p.

ABSTRACT:

Background

The anti-tumor effect of interleukin (IL)-36β-mediated activation of CD8⁺ T cells has been reported, but the molecular mechanism is largely undefined.

Methods

The levels of IL-36β in pancreatic cancer were examined by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36β on the growth of pancreatic cancer cells. We then examined the changes of CD8⁺ T cells and natural killer (NK) cells in the tumor by flow cytometry. The microRNA expression profiles were determined by microarray analysis.

Results

The results revealed decreased levels of IL-36β in pancreatic cancer tissues. In addition, IL-36β inhibited tumor growth and promoted CD8⁺ T and NK cell proliferation in the tumor microenvironment (TME). Moreover, IL-36β stimulated CD8⁺ T cells to synthesize high amounts of interferon-gamma (IFN-γ) and IL-2. Microarray analysis showed that IL-36β administration to human and mouse CD8⁺ T cells consistently downregulated the miRNA, let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8⁺ T cells, whereas its upregulation had the opposite effect. Further experiments demonstrated that IL-36β downregulated IFN-γ in let-7c-5p⁺ CD8⁺ T cells.

Conclusions

These findings suggest IL-36β promotes IFN-γ and IL-2 production in CD8⁺ T cells, as well as anti-tumor effects in CD8⁺ T cells by downregulating let-7c-5p.

SUBMITTER: Li D

PROVIDER: S-EPMC8743712 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-36β promotes anti-tumor effects in CD8<sup>+</sup> T cells by downregulating micro-RNA let-7c-5p.

Li Dongbao D Huang Yang Y Yu Zhuwen Z Zhang Jianglei J Hu Chenrui C Bai Yanjin Y Wang Jin J Zhang Zhe Z Ouyang Jun J Zhou Jin J Zhao Xin X

Annals of translational medicine 20211201 23

<h4>Background</h4>The anti-tumor effect of interleukin (IL)-36β-mediated activation of CD8<sup>+</sup> T cells has been reported, but the molecular mechanism is largely undefined.<h4>Methods</h4>The levels of IL-36β in pancreatic cancer were examined by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36β on the growth of pancreatic cancer cells. We then examined the changes of CD8<sup>+</sup> T cell ...[more]

PMID: 35071428

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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

IL-36β promotes anti-tumor effects in CD8⁺ T cells by downregulating micro-RNA let-7c-5p.

Background

Methods

Results

Conclusions

Publications

IL-36β promotes anti-tumor effects in CD8<sup>+</sup> T cells by downregulating micro-RNA let-7c-5p.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

IL-36β promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.

Background

Methods

Results

Conclusions

Publications

IL-36β promotes anti-tumor effects in CD8<sup>+</sup> T cells by downregulating micro-RNA let-7c-5p.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

IL-36β promotes anti-tumor effects in CD8⁺ T cells by downregulating micro-RNA let-7c-5p.