| First Author | Sasaki I | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 4 | Pages | 113981 |
| PubMed ID | 38520688 | Mgi Jnum | J:349724 |
| Mgi Id | MGI:7627927 | Doi | 10.1016/j.celrep.2024.113981 |
| Citation | Sasaki I, et al. (2024) A stress sensor, IRE1alpha, is required for bacterial-exotoxin-induced interleukin-1beta production in tissue-resident macrophages. Cell Rep 43(4):113981 |
| abstractText | Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1beta (IL-1beta), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1alpha), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1beta production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1alpha-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1beta production, indicating that IRE1alpha is required for CT- or CTB-induced IL-1beta production in RPMs. This study demonstrates the critical roles of IRE1alpha in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages. |
