RRC ID 49555
Author Takahashi Y, Sato S, Kurashima Y, Lai CY, Otsu M, Hayashi M, Yamaguchi T, Kiyono H.
Title Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells.
Journal EBioMedicine
Abstract Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs) and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium-mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis.
Volume 23
Pages 34-45
Published 2017-9-1
DOI 10.1016/j.ebiom.2017.07.027
PII S2352-3964(17)30302-X
PMID 28789943
PMC PMC5605307
MeSH Adipocytes / cytology Adipocytes / metabolism* Adipose Tissue / cytology Adipose Tissue / metabolism Animals Cell Line Cells, Cultured Coculture Techniques Disease Models, Animal Epithelial Cells / metabolism* Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism Inflammatory Bowel Diseases / immunology Inflammatory Bowel Diseases / metabolism Inflammatory Bowel Diseases / pathology Intestinal Mucosa / immunology* Intestinal Mucosa / metabolism* Intestinal Mucosa / pathology Male Mice NF-kappa B / metabolism STAT3 Transcription Factor Signal Transduction*
IF 5.736
Times Cited 14
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).