Transcriptomics

Dataset Information

0

Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages


ABSTRACT: A wide variety of electrophilic derivatives of the Kreb’s cycle-derived metabolite, itaconate, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production. Endogenous itaconate directly targets cysteine 13 in IRAK4 disrupting IRAK4 autophosphorylation and activation, drives the degradation of NFκB, and modulates global ubiquitination patterns. As a result, cells unable to make itaconate overproduce inflammatory cytokines such as TNFα, IL6, and IL-1β in response to these innate activators. In contrast, the production of IFNβ, downstream of LPS, requires the production of itaconate. These data demonstrate that itaconate is a critical arbiter of inflammatory cytokine production downstream of multiple innate signaling pathways laying the groundwork for the development of itaconate mimetics for the treatment of autoimmunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272396 | GEO | 2024/07/17

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-07-16 | PXD053956 | JPOST Repository
2016-07-01 | E-GEOD-82043 | biostudies-arrayexpress
2017-10-12 | GSE86234 | GEO
2010-10-23 | E-GEOD-24894 | biostudies-arrayexpress
2016-07-01 | GSE82043 | GEO
2021-01-01 | GSE160307 | GEO
2023-01-01 | GSE215195 | GEO
2024-07-08 | GSE230735 | GEO
2010-05-19 | E-FPMI-7 | biostudies-arrayexpress
2010-10-23 | GSE24894 | GEO