E-resources
Peer reviewed
-
He, Kaixin; Wan, Tingting; Wang, Decai; Hu, Ji; Zhou, Tingyue; Tao, Wanyin; Wei, Zheng; Lu, Qiao; Zhou, Rongbin; Tian, Zhigang; Flavell, Richard A.; Zhu, Shu
Cell, 07/2023, Volume: 186, Issue: 14Journal Article
The intestinal epithelial cells (IECs) constitute the primary barrier between host cells and numerous foreign antigens; it is unclear how IECs induce the protective immunity against pathogens while maintaining the immune tolerance to food. Here, we found IECs accumulate a less recognized 13-kD N-terminal fragment of GSDMD that is cleaved by caspase-3/7 in response to dietary antigens. Unlike the 30-kD GSDMD cleavage fragment that executes pyroptosis, the IEC-accumulated GSDMD cleavage fragment translocates to the nucleus and induces the transcription of CIITA and MHCII molecules, which in turn induces the Tr1 cells in upper small intestine. Mice treated with a caspase-3/7 inhibitor, mice with GSDMD mutation resistant to caspase-3/7 cleavage, mice with MHCII deficiency in IECs, and mice with Tr1 deficiency all displayed a disrupted food tolerance phenotype. Our study supports that differential cleavage of GSDMD can be understood as a regulatory hub controlling immunity versus tolerance in the small intestine. Display omitted •Dietary antigens induce a non-pyroptotic 13kD GSDMD fragment in the upper small intestine•Caspase-3 and -7 cleave GSDMD at D88 in duodenum IECs in response to dietary antigens•Nuclear-localized GSDMD fragment regulates CIITA and MHCII in IECs to induce Tr1 cells•Inactivation of food-induced GSDMD cleavage in IECs disrupts immune tolerance to food Dietary-antigen-dependent cleavage of Gasdermin D maintains food tolerance irrespective of pyroptosis.
Author
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.