Abstract: The innate immune response within cytosolic compartments is pivotal for safeguarding barrier tissues like skin. Key players in this defense mechanism are NOD1 and NOD2, intracellular sensors specialized in detecting small fragments of bacterial cell wall peptidoglycans known as muropeptides. These muropeptides find their way into cells, particularly epithelial cells, although the precise mechanisms remain elusive. Our research has pointed towards SLC46 transporters as facilitators of muropeptide transportation in Drosophila immunity. Notably, among the SLC46 family members, Slc46a2 stands out as a critical player in delivering diaminopimelic acid (DAP)-muropeptides, consequently activating NOD1 in skin keratinocytes.

In mouse models, the absence of Slc46a2 and Nod1 significantly dampened psoriatic inflammation. This phenomenon was further underscored by the central roles of Caspase1 and GasderminD within this pathway. Taken together, these studies highlight SLC46A2 as a transporter responsible for delivering NOD1-activating muropeptides, essential for maintaining the integrity of the skin barrier. Additionally, this transporter emerges as a promising target for interventions aimed at mitigating inflammation.

Meeting ID: 982 6878 3362
Passcode: 670455