Left to right: Prof. Jesús Vázquez, Prof. Francisco Sánchez-Madrid, Dr. Danay Cibrián, and Dr. Pilar Martín. Seated, left to right: María Laura Sáiz, Dr. Hortensia de la Fuente, Dr. Alessia Ferrarini, Dr. Inmaculada Jorge, Raquel Sánchez-Díaz, and Olga Moreno-Gonzalo. Courtesy CNIC
Scientists have defined the key role of an immune-system receptor in the development of psoriasis, and suggest that it could serve as a therapeutic target for the control of this condition, according to a study published in Nature Immunology (July 4, 2016).
The study established the role of the leukocyte activation receptor CD69 in the control of aminoacid uptake, activation of the aryl hydrocarbon receptor (AhR), and the expression of inflammatory interleukins (IL) such as IL-22 in gamma delta and Th17 T cells, indicating that CD69 contributes to the development of psoriasis.
“The skin contains many populations of specialized immune cells that act together to guarantee defense and protection,” said Dr. Francisco Sánchez-Madrid, head of the Intercellular Communication group at the Centro de Investigaciones Cardiovasculares Carlos III (CNIC) in Madrid and a study author, in a press release. The leukocyte activation receptor CD69 is present in inflammatory cells in the skin, he added.
“These cells consume free essential aminoacids like tryptophan by using specialized transport systems present in the cell membrane, such as LAT1 (SLc7a5),” he said. “Consumption of aminoacids by inflammatory cells in the skin increases sharply during the inflammatory reaction because it is important for their proliferation and activation and for the secretion of inflammatory molecules that amplify tissue damage, like IL-22 and IL-17.”
Using mice whose immune cells lack CD69, the research team showed that the expression of this molecule is important for the development of psoriasis.
“We found that CD69 associates in the cell membrane with LAT1, regulating its level of expression and the uptake of aminoacids such as tryptophan,” said Dr. Danay Cibrián, a study investigator with CNIC, adding that “tryptophan metabolism generates intermediate metabolites that activate the AhR, which in turn regulates the expression of inflammatory interleukins such as IL-22. Increases in the circulating levels of tryptophan favour the development of psoriasis by leading to increased levels of IL-22 in the skin.”
The importance of tryptophan metabolism in the secretion of the interleukins that mediate the development of psoriasis has been demonstrated in patient studies.
The researchers concluded that their study demonstrates the importance of CD69 in the development of psoriasis and opens the way to its possible use as a future therapeutic target for treatment.