CD69 controls L-Trp uptake through LAT1-CD98 and AhR-dependent IL-22 secretion in psoriasis

The activation marker CD69 is expressed by skin γδ T cells. Here we demonstrate that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent interleukin 22 (IL-22) secretion in γδ T cells, which contributed to psoriasis development induced by IL-23. CD69 associated with the aromatic amino acid transporter complex LAT1-CD98 and regulated its surface expression, L-tryptophan (L-Trp) uptake and intracellular quantity of L-Trp-derived AhR activators. In vivo administration of L-Trp, an AhR inhibitor or IL-22 abrogated differences in skin inflammation between CD69-deficient and wild type mice. LAT1-mediated regulation of AhR activation and IL-22 secretion was also observed in circulating Vγ9 γδ T cells of psoriatic patients. Thus, CD69 is a key mediator of the pathogenesis of psoriasis by controlling LAT1-CD98-mediated metabolic cues.