Immune receptor found to play key role in psoriasis development

John Murphy, MDLinx | July 05, 2016

Investigators have found that the immune-system receptor CD69 plays a key role in the development of psoriasis, which suggests that this receptor could be a therapeutic target for treating this disease, according to a study published July 4, 2016 in the journal Nature Immunology.

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Pathogenesis of psoriasis

CD69, an immune-system receptor, plays an important role in the development of psoriasis—and may be a therapeutic target to treat it. (Photo: Eisfelder; CC BY-SA 3.0)

The researchers already knew that CD69, a leukocyte activation receptor, was present in inflammatory cells in the skin. But they weren’t sure what role, if any, CD69 played in the pathogenesis of psoriasis.

To find out, the scientists tested mice whose skin immune cells were deficient in CD69. The researchers injected the pro-inflammatory cytokine interleukin 23 (IL-23) into both CD69-deficient mice and wild-type mice to produce a psoriasis-like inflammatory reaction.

After the injections, the CD69-deficient mice developed much less swell­ing, epidermal acanthosis, dermal inflammation, and keratinocyte proliferation than the wild-type mice. “These results indicated that the absence of CD69 prevented the development of psoriasis after intradermal injection of IL-23,” the authors concluded. This finding suggested that CD69 exerted an immunomodulatory effect on pso­riasis.

“We found that CD69 associates in the cell membrane with L-type amino acid transporter 1 (LAT1), regulating its level of expression and the uptake of amino acids such as tryptophan,” explained study researcher Danay Cibrián, PhD, of the Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), in Madrid, Spain.

“Increases in the circulating levels of tryptophan favor the development of psoriasis by leading to increased levels of IL-22 in the skin,” Dr. Cibrián added.

The researchers concluded that this study demonstrates that CD69 plays an important role in the development of psoriasis. This discovery also opens the door to its possible use as a future therapeutic target for the treatment of this chronic inflammatory disease, which currently has no cure.

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