The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10–producing regulatory B cells
Open accessAbstract
Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.
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“The gut microbiota also activated intestinal cells that produce IL-10 in MyD88/TLR2/ PI3K-dependent pathways to maintain mucosal homeostasis.123”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [123]
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“Moreover, it was shown that resident microbiota also stimulated the regulatory capacity of B cells to reduce colonic T cell activation, maintaining mucosal homeostasis [48].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [48]
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Cites
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
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Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
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The regulation of IL-10 production by immune cells
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Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
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The Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead
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The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604
IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6
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Treatment of Murine Colitis by Lactococcus lactis Secreting Interleukin-10
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Federici, S., Kredo-Russo, S., Valdés-Mas, R., Kviatcovsky, D., Weinstock, E., Matiuhin, Y., Silberberg, Y., Atarashi, K., Furuichi, M., Oka, A., et al. (2022) · Cell · doi:10.1016/j.cell.2022.07.003 · Cited by 542
Self-citationIntestinal flora and disease mutually shape the regional immune system in the intestinal tract
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Metadata
- Authors
- Mishima, Y., Oka, A., Liu, B., Herzog, J. W., Eun, C. S., Fan, T.-J., Bulik-Sullivan, E., Carroll, I. M., Hansen, J. J., Chen, L., Wilson, J. E., Fisher, N. C., Ting, J. P. Y., Nochi, T., Wahl, A., Garcia, J. V., Karp, C. L., & Sartor, R. B.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- UNC Lineberger Comprehensive Cancer Center (US)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Sartor, R. Balfour
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2019-08-05
- Volume
- 129
- Issue
- 9
- Pages
- 3702-3716
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC6715367
- OpenAlex
- W2950835870
- Cited by
- 166
- References
- 56
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 22 · 2023: 28 · 2022: 27 · 2021: 31 · 2020: 27 · 2019: 5
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Crohn’s and Colitis Foundation (Microbiome Initiative (RBS),Gnotobiotic Facility (RBS), Research Fellowship Award (YM,AO))
- the American Cancer Society (PF-13-401-01-TBE.)
- NIH (P01 DK094779,R01 DK53347,P40 OD010995,P30 DK34987 (RBS),R01 CA156330 (JPYT), R01 AI123010 (AW),R01 AI111899,Al140799,MH108179 (JVG))
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- gut microbiota, intestinal homeostasis, IL-10-producing B cells, regulatory B cells, TLR2, MyD88, PI3K signaling, Akt, T cell-mediated colitis, mucosal inflammation, bacterial extracts, fecal microbiota transplantation, germ-free mice
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Colitis, Germ-Free Life, Immunity, Innate, Inflammation, Intestines, Mice, Inbred C57BL, Down-Regulation, Cytokines, Interleukin-10, Mice, Knockout, Phosphatidylinositol 3-Kinases, Green Fluorescent Proteins, Toll-Like Receptor 2, Toll-Like Receptor 9, Mice, Myeloid Differentiation Factor 88, B-Lymphocytes, Regulatory
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