title: Adenomatous polyps are driven by microbe-instigated focal inflammation and are controlled by IL-10-producing T cells.
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.
authors: Authors' Affiliations: Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine; Department of Medicine, Knapp Center for Biomedical Discovery; Department of Ecology and Evolution, University of Chicago, Chicago; Argonne National Laboratory, Argonne, Illinois; Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama; Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arkansas; and Institute for Immunology, Technical University Dresden, Dresden, Germany.
authors: Kristen L
authors: KL
authors: Dennis
authors: Yunwei
authors: Y
authors: Wang
authors: Nichole R
authors: NR
authors: Blatner
authors: Shuya
authors: S
authors: Wang
authors: Abdulrahman
authors: A
authors: Saadalla
authors: Erin
authors: E
authors: Trudeau
authors: Axel
authors: A
authors: Roers
authors: Casey T
authors: CT
authors: Weaver
authors: James J
authors: JJ
authors: Lee
authors: Jack A
authors: JA
authors: Gilbert
authors: Eugene B
authors: EB
authors: Chang
authors: Khashayarsha
authors: K
authors: Khazaie
mesh_terms: D018256:Adenomatous Polyps / Q000209:etiology* / Q000473:pathology; D019264:Adoptive Transfer; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007108:Immune Tolerance; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D016753:Interleukin-10 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D004269:DNA, Bacterial; C556062:IL10 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10
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