Asset Details
Do you wish to reserve the book?
Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis
Do you wish to request the book?
Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Intestinal epithelial damage-derived mtDNA activates STING-IL12 axis in dendritic cells to promote colitis
2024
Overview
The treatment of ulcerative colitis (UC) presents an ongoing clinical challenge. Emerging research has implicated that the cGAS-STING pathway promotes the progression of UC, but conflicting results have hindered the development of STING as a therapeutic target. In the current study, we aim to comprehensively elucidate the origins, downstream signaling and pathogenic roles of myeloid STING in colitis and colitis-associated carcinoma (CAC).
mice were constructed for inducible myeloid-specific deletion of STING. RNA-sequencing, flow cytometry, and multiplex immunohistochemistry were employed to investigate immune responses in DSS-induced colitis or AOM/DSS-induced carcinogenesis. Colonic organoids, primary bone marrow derived macrophages and dendritic cells, and splenic T cells were used for
studies.
We observed that myeloid STING knockout in adult mice inhibited macrophage maturation, reduced DC cell activation, and suppressed pro-inflammatory Th1 and Th17 cells, thereby protecting against both acute and chronic colitis and CAC. However, myeloid STING deletion in neonatal or tumor-present mice exhibited impaired immune tolerance and anti-tumor immunity. Furthermore, we found that TFAM-associated mtDNA released from damaged colonic organoids, rather than bacterial products, activates STING in dendritic cells in an extracellular vesicle-independent yet endocytosis-dependent manner. Both IRF3 and NF-κB are required for STING-mediated expression of IL-12 family cytokines, promoting Th1 and Th17 differentiation and contributing to excessive inflammation in colitis.
Detection of the TFAM-mtDNA complex from damaged intestinal epithelium by myeloid STING exacerbates colitis through IL-12 cytokines, providing new evidence to support the development of STING as a therapeutic target for UC and CAC.
Publisher
Ivyspring International Publisher
Subject
/ Colitis - chemically induced
/ Colitis, Ulcerative - genetics
/ Colitis, Ulcerative - immunology
/ Colitis, Ulcerative - metabolism
/ Colitis, Ulcerative - pathology
/ Colitis-Associated Neoplasms - genetics
/ Colitis-Associated Neoplasms - immunology
/ Colitis-Associated Neoplasms - metabolism
/ Colitis-Associated Neoplasms - pathology
/ Dendritic Cells - immunology
/ Dendritic Cells - metabolism
/ DNA, Mitochondrial - genetics
/ DNA, Mitochondrial - metabolism
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Mice
