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Berberine Promotes Induction of Immunological Tolerance to an Allograft via Downregulating Memory CD8+ T-Cells Through Altering the Gut Microbiota.
- Source :
- Frontiers in Immunology; 2/12/2021, Vol. 11, pN.PAG-N.PAG, 13p
- Publication Year :
- 2021
-
Abstract
- 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<superscript>+</superscript> 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<superscript>+</superscript>CD44<superscript>high</superscript>CD62L<superscript>low</superscript> and central memory CD8<superscript>+</superscript>CD44<superscript>high</superscript>CD62L<superscript>high</superscript> T-cells (T<subscript>CM</subscript>), 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<superscript>+</superscript> T<subscript>CM</subscript> cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8<superscript>+</superscript> T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8<superscript>+</superscript> T<subscript>CM</subscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- GUT microbiome
BERBERINE
IMMUNOLOGICAL tolerance
T cells
LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 148717559
- Full Text :
- https://doi.org/10.3389/fimmu.2021.646831