Tmem178 Negatively Regulates Interleukin (IL) ‐1β Production Through Inhibition of the NLRP3 Inflammasome
Authors' conclusion
Down-regulation of TMEM178 levels may represent a marker of disease activity and help identify patients who could benefit from inflammasome targeting.
Study context
- Population
- Mouse macrophages and Perforin-/-/Tmem178-/- mice with lymphocytic choriomeningitis virus (LCMV)-induced cytokine storm syndrome (CSS); human data sets of patients with active systemic juvenile idiopathic arthritis (sJIA) and healthy controls
- Comparison
- Tmem178-/- vs wild-type (WT) macrophages and mice; patients with active sJIA vs healthy controls
Methodological detailsin vitro macrophage experiments, LCMV-induced CSS mouse model, human transcript data sets
- In vitro macrophage experiments
- LCMV-induced CSS mouse model
- Human transcript data sets
Main finding
As reported in the abstract
- TMEM178 levels reduced and IL1B levels increased in whole blood and monocytes from patients with sJIA
- Tmem178-/- macrophages produce elevated IL-1β vs WT cells
- Elevated intracellular calcium after store-operated calcium entry (SOCE) activation in Tmem178-/- macrophages induces mitochondrial damage, mitochondrial reactive oxygen species (mtROS) release and NLRP3 inflammasome activation
- In vivo, inflammasome inhibition or IL-1β neutralization prolongs Tmem178-/- mouse survival in LCMV-induced CSS
Original publication
Tmem178 Negatively Regulates IL ‐1β Production Through Inhibition of the NLRP3 Inflammasome. Arthritis Rheumatol. Published 13 November 2023. doi:10.
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