metallothionein and Adenomatous-Polyposis-Coli

Intestinal epithelial cells (IECs) regulate intestinal immune cells, particularly development of T-helper 17 (Th17) cells. Deregulation of this process leads to intestinal inflammation and tumorigenesis, via unknown mechanisms. TANK-binding kinase 1 (TBK1) is expressed by IECs and cells in the innate immune system. We studied the functions of TBK1 in the intestinal immune response and tumorigenesis in mice.. We performed studies of wild-type mice, mice with conditional disruption of Tbk1 (Tbk1. Compared to Apc. Expression of TBK1 by IECs suppresses expression of MT1 and prevents expression of IL1β by macrophages and differentiation of Th17 cells, to prevent inflammation and tumorigenesis. Strategies to block this pathway might be developed for colorectal tumorigenesis.

Topics: Adenomatous Polyposis Coli; Animals; Cell Differentiation; Cell Transformation, Neoplastic; Cells, Cultured; Coculture Techniques; Disease Models, Animal; Epithelial Cells; Genes, APC; Humans; Immunity, Innate; Immunity, Mucosal; Interleukin-17; Interleukin-1beta; Intestinal Mucosa; Intestinal Neoplasms; Macrophages; Metallothionein; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Protein Serine-Threonine Kinases; Th17 Cells