PUBLICATION
Apical extrusion prevents apoptosis from activating an acute inflammatory program in epithelia
- Authors
- Duszyc, K., von Pein, J.B., Ramnath, D., Currin-Ross, D., Verma, S., Lim, F., Sweet, M.J., Schroder, K., Yap, A.S.
- ID
- ZDB-PUB-230831-51
- Date
- 2023
- Source
- Developmental Cell 58(21): 2235-2248.e6 (Journal)
- Registered Authors
- Duszyc, Kinga, Verma, Suzie, Yap, Alpha
- Keywords
- acute inflammation, apical extrusion, apoptosis, epithelial homeostasis
- MeSH Terms
-
- Animals
- Apoptosis*/physiology
- Cell Death
- Epithelium
- Inflammation
- Zebrafish*
- PubMed
- 37647898 Full text @ Dev. Cell
Citation
Duszyc, K., von Pein, J.B., Ramnath, D., Currin-Ross, D., Verma, S., Lim, F., Sweet, M.J., Schroder, K., Yap, A.S. (2023) Apical extrusion prevents apoptosis from activating an acute inflammatory program in epithelia. Developmental Cell. 58(21):2235-2248.e6.
Abstract
Apoptosis is traditionally considered to be an immunologically silent form of cell death. Multiple mechanisms exist to ensure that apoptosis does not stimulate the immune system to cause inflammation or autoimmunity. Against this expectation, we now report that epithelia are programmed to provoke, rather than suppress, inflammation in response to apoptosis. We found that an acute inflammatory response led by neutrophils occurs in zebrafish and cell culture when apoptotic epithelial cells cannot be expelled from the monolayer by apical extrusion. This reflects an intrinsic circuit where ATP released from apoptotic cells stimulates epithelial cells in the immediate vicinity to produce interleukin-8 (IL-8). Apical extrusion therefore prevents inappropriate epithelial inflammation by physically eliminating apoptotic cells before they can activate this pro-inflammatory circuit. This carries the implication that epithelia may be predisposed to inflammation, elicited by sporadic or induced apoptosis, if apical extrusion is compromised.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping