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

被引：92

作者：

Cibrian, Danay ^{[1
]}

Laura Saiz, Maria ^{[1
]}

de la Fuente, Hortensia ^{[1
]}

Sanchez-Diaz, Raquel ^{[2
]}

Moreno-Gonzalo, Olga ^{[1
]}

Jorge, Inmaculada ^{[2
]}

Ferrarini, Alessia ^{[2
]}

Vazquez, Jesus ^{[2
]}

Punzon, Carmen ^{[3
]}

Fresno, Manuel ^{[3
]}

Vicente-Manzanares, Miguel ^{[1
]}

Dauden, Esteban ^{[4
]}

Fernandez-Salguero, Pedro M. ^{[5
]}

Martin, Pilar ^{[2
]}

Sanchez-Madrid, Francisco ^{[1
,2
]}

机构：

[1] Univ Autonoma Madrid, Hosp Princesa, Immunol Serv, Madrid, Spain

[2] Ctr Nacl Invest Cardiovasc, Dept Vasc Biol & Inflammat, Madrid, Spain

[3] Univ Autonoma Madrid, Dept Mol Biol, Ctr Biol Mol Severo Ochoa, Madrid, Spain

[4] Hosp Princesa, Dermatol Serv, Madrid, Spain

[5] Univ Extremadura, Fac Sci, Dept Biochem Mol Biol & Genet, Badajoz, Spain

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 08期

基金：

欧洲研究理事会;

关键词：

ARYL-HYDROCARBON RECEPTOR; DELTA T-CELLS; AMINO-ACID-TRANSPORT; EPIDERMAL DIFFERENTIATION; PHYSIOLOGICAL-ROLE; SKIN INFLAMMATION; POTENTIAL ROLE; GAMMA; MICE; MECHANISMS;

D O I：

10.1038/ni.3504

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The activation marker CD69 is expressed by skin gamma delta T cells. Here we found that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent secretion of interleukin 22 (IL-22) by gamma delta 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 V(gamma)9(+) gamma delta T cells of psoriatic patients. Thus, CD69 serves as a key mediator of the pathogenesis of psoriasis by controlling LAT1-CD98-mediated metabolic cues.

引用

页码：985 / +

页数：15

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