Format

Send to

Choose Destination
Nat Immunol. 2016 Aug;17(8):985-96. doi: 10.1038/ni.3504. Epub 2016 Jul 4.

CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis.

Author information

1
Immunology Service, Hospital de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa, Madrid, Spain.
2
Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
3
Department of Molecular Biology, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, Spain.
4
Dermatology Service, Hospital de la Princesa, Madrid, Spain.
5
Department of Biochemistry, Molecular Biology and Genetic, Faculty of Sciences, University of Extremadura, Badajoz, Spain.

Abstract

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

PMID:
27376471
PMCID:
PMC5146640
DOI:
10.1038/ni.3504
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center