When SLC46A2 delivers cargo into keratinocytes

How pattern recognition receptors NOD1 and NOD2 sense bacterial muropeptides from extracellular bacteria to drive keratinocyte inflammation remains unclear. In this issue of Immunity, Bharadwaj et al. show that the solute carrier 46A2 (SLC46A2) delivers DAP-muropeptides into the cytosol to drive NOD1 activation in keratinocytes and elicit skin inflammation during psoriasis. How pattern recognition receptors NOD1 and NOD2 sense bacterial muropeptides from extracellular bacteria to drive keratinocyte inflammation remains unclear. In this issue of Immunity, Bharadwaj et al. show that the solute carrier 46A2 (SLC46A2) delivers DAP-muropeptides into the cytosol to drive NOD1 activation in keratinocytes and elicit skin inflammation during psoriasis. Methotrexate suppresses psoriatic skin inflammation by inhibiting muropeptide transporter SLC46A2 activityBharadwaj et al.ImmunityApril 27, 2023In BriefInnate immune receptors NOD1/2 detect bacterial peptidoglycans that access the cytosol. However, the mechanisms by which peptidoglycan fragments reach the cytosol are unclear. Bharadwaj et al. reveal that Slc46a2 is critical for transporting DAP-type peptidoglycans into keratinocytes, inhibited by the anti-inflammatory methotrexate, and works with the NOD1 pathway to incite psoriatic inflammation. Full-Text PDF Open Access