Adenomatous Polyps Are Driven by Microbe-Instigated Focal Inflammation and Are Controlled by IL-10–Producing T Cells
Kristen L. Dennis,Yunwei Wang,Nichole R. Blatner,Shuya Wang,Abdulrahman Saadalla,Erin Trudeau,Axel Roers,Casey T. Weaver,James J. Lee,Jack A. Gilbert,Eugene B. Chang,Khashayarsha Khazaie +11 more
TLDR
It is established that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses, which are suppressed by IL-10 derived specifically from T cells and Tregs.Abstract:
Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune tolerance and tumor growth. Defying these expectations, the adoptive transfer of IL-10-expressing T cells to mice with polyposis attenuates microbial-induced inflammation and suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated IL-10 in T cells in APC(Δ468) mice and compared the effects of treatment with broad-spectrum antibiotics. We found that T cells and regulatory T cells (Treg) were a major cellular source of IL-10 in both the healthy and polyp-bearing colon. Notably, T cell-specific ablation of IL-10 produced pathologies that were identical to mice with a systemic deficiency in IL-10, in both cases increasing the numbers and growth of colon polyps. Eosinophils were found to densely infiltrate colon polyps, which were enriched similarly for microbiota associated previously with colon cancer. In mice receiving broad-spectrum antibiotics, we observed reductions in microbiota, inflammation, and polyposis. Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs.read more
Citations
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Macrophage IL-10 Blocks CD8+ T Cell-Dependent Responses to Chemotherapy by Suppressing IL-12 Expression in Intratumoral Dendritic Cells
Brian Ruffell,Debbie Chang-Strachan,Vivien W. Chan,Alexander Rosenbusch,Alexander Rosenbusch,Christine M.T. Ho,Nancy Pryer,Dylan Daniel,E. Shelley Hwang,Hope S. Rugo,Lisa M. Coussens +10 more
TL;DR: Interleukin (IL)-10 expression by macrophages is identified as the critical mediator of this phenotype and expression of IL12A and cytotoxic effector molecules were predictive of pathological complete response rates to paclitaxel in human breast cancer.
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The Intestinal Microbiota in Colorectal Cancer
TL;DR: Large metagenomic studies in human CRC associated microbiome signatures with the colorectal adenoma-carcinoma sequence suggest a fundamental role of the intestinal microbiota in the evolution of gastrointestinal malignancy.
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Performance and Microbial Community Analysis of a Novel DEAMOX Based on Partial-Denitrification and Anammox Treating Ammonia and Nitrate Wastewaters
TL;DR: High-throughput sequencing analysis revealed that Thauera genera were dominant in both SBRs and possibly played a key role for partial-denitrification with high NO2--N accumulation and the Denitratisoma capable of complete denitrification (NO3--N→N2) was found in R2 that might lead to lower NTR.
Journal ArticleDOI
Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome
Israr Khan,Naeem Ullah,Zha Lajia,Bai Yanrui,Ashiq Khan,Tang Zhao,Tuanjie Che,Chunjiang Zhang +7 more
TL;DR: The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented, which suggests that well-designed randomized control trials and mouse models are required for further research.
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Dietary fucoidan modulates the gut microbiota in mice by increasing the abundance of Lactobacillus and Ruminococcaceae
TL;DR: Modulations of gut microbiota by different fucoidans were studied and it was found that at the expense of opportunistic pathogenic bacteria such as Peptococcus, the abundance of beneficial bacteria was significantly increased in response to fucoidan treatment.
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