Scientists identify an essential role of the immune receptor CD69 in psoriasis

July 04, 2016

Scientists at the Centro de Investigaciones Cardiovasculares Carlos III (CNIC) have defined the key role of an immune-system receptor in the development of psoriasis, suggesting that it could serve as a therapeutic target for the control of this disease. The study was carried out by Dr. Danay Cibrián and directed by Dr. Francisco Sánchez-Madrid, who heads the Intercellular Communication group at the CNIC. The study establishes 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 such as IL-22 in gamma delta and Th17 T cells, indicating that CD69 contributes to the development of psoriasis. The study, published in Nature Immunology, also indicates that CD69 might also participate in other inflammatory diseases such as aterosclerosis.

Psoriasis is a chronic inflammatory disease of the skin that affects approximately 2-3% of the world population and has a negative impact on patients' physical and mental health. The prevalence of psoriasis in Spain has increased by 1% in the last 15 years, and the disease now affects an estimated 1 million people across the country.

The skin is the first line of defense against many kinds of infection, trauma, and radiation. Dr. Francisco Sánchez-Madrid explains that "the skin contains many populations of specialized immune cells that act together to guarantee defense and protection." The leukocyte activation receptor CD69 is present in inflammatory cells in the skin. Dr. Francisco Sánchez-Madrid continues "These cells consume free essential aminoacids like tryptophan by using specialized transport systems present in the cell membrane, such as LAT1 (SLc7a5). 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 interleukins 22 and 17 (IL-22 and IL-17)."

Tryptophan


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," explains Dr. Danay Cibrián, 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 favor 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 conclude 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 the treatment of this disease.

The research was led by Dr. Francisco Sánchez-Madrid, Profesor at the Universidad Autónoma de Madrid and Head of the Immunology Service at the la Princesa University Hospital, and was conducted through collaborations with CNIC researcher Dr. Pilar Martín, the CNIC Proteomics Unit, directed by Prof. Jesús Vázquez, the Dermatology Service at La Princesa university hospital, directed by Dr. Esteban Daudén, and Professor Manuel Fresno of the Centro de Biología Molecular Severo Ochoa in Madrid.
-end-


Centro Nacional de Investigaciones Cardiovasculares

Related Psoriasis Articles from Brightsurf:

Most psoriasis patients taking immunosuppressants survive COVID-19
Patients with psoriasis who are taking drugs that affect their immune system have high rates of survival from COVID-19.

Getting under the skin of psoriasis
Psoriasis afflicts millions of people worldwide, but treatments are limited to small molecules like steroids, which can cause skin thinning and lose their effectiveness over time.

Psoriasis patients' mental health is more than skin-deep
A new study from Umeå University, Sweden, shows that other somatic diseases have even more impact on patients' mental health than their skin symptoms, highlighting the importance of holistic patient care.

Psoriasis: Towards a novel therapeutic approach
Researchers at the Université libre de Bruxelles (ULB) and the Department of Dermatology of the Erasme hospital uncover the importance of VEGFA signaling in the epidermis to mediate psoriasis development.

Insights into psoriasis suggest a new treatment target
Investigators from Brigham and Women's Hospital and the Harvard Stem Cell Institute have uncovered a novel pathway that may explain why skin thickens in psoriasis and suggests new strategies for developing therapies for the condition.

Psoriasis onset determines if psoriatic arthritis patients develop arthritis or psoriasis first
In a new study presented at the 2019 ACR/ARP Annual Meeting, researchers found the age of psoriasis onset determines whether arthritis or psoriasis starts first in people with psoriatic arthritis.

Study: Some biologic treatments for psoriasis may be safer for patients
In the largest study of its kind, Erica D. Dommasch, M.D., M.P.H., a dermatologist in the Department of Dermatology at BIDMC, and colleagues found a decreased risk of infection in patients with psoriasis using some of the newer, more targeted medications compared to those taking methotrexate, a drug widely used since the 1960s as a first line treatment for moderate-to-severe psoriasis.

Higher weight increases risk of psoriasis
The higher a person's BMI, the greater the chance of getting psoriasis.

Lipid that aids normal skin turnover may help psoriasis
Topical application of the lipid phosphatidylglycerol, or PG, on a mouse model of psoriasis reduced inflammation as well as characteristic, raised skin lesions, they report in the Journal of Investigative Dermatology.

New insight into the mechanism of the drug against sclerosis and psoriasis
A multidisciplinary research team at Aarhus University has provided fundamental new insight into the mechanism of the medical drug dimethyl fumarate, which is the active component of important treatments for multiple sclerosis and psoriasis.

Read More: Psoriasis News and Psoriasis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.