Wang Honglin revealed the new mechanism of viral infection in the pathophysiology of psoriasis

Recently, Wang Honglin and his group from Shanghai Jiao Tong University College of Basic Medicine have revealed the virus infection plays an important role in triggering psoriasis(psoriasis vulgaris), breaking the generally accepted idea in the past that psoriasis is caused by bacteria especially by streptococcus. The study is the first to report the virus may be the key factors causing psoriasis, which probably provides new ideas for effective prevention and treatment of psoriasis. The results were published online on EMBO Molecular Medicineon April 4, an international journal of European Molecular Biology.

Skin, the largest organ of the human body, directlyexposed to the external environment, is the first barrier for the body to resist mechanical damage and microbial infection, which is of key importance to maintain the immune homeostasis in the body. Psoriasis is a common immune-mediated chronic inflammatory skin disorder, and has affected 1 to 3 percent of the world‘s population (145 million), 800 to 10 millions of which are in China. Psoriasis can not only involve the skin and whole body, seriously affecting the quality of patient’s life, but can cause various complications, the most common of which are metabolic syndrome, cardiovascular disease and psoriatic arthritis. In 2013, the World Health Organization(WHO) listed psoriasis as one of global health issues at its 67th general assembly. It has been recently reported that the pathogenesis of psoriasis is associated with heredity facotrs and external environment, but its etiological mechanism is still unknown.

Retinoic acid induced-gene I (RIG-I, gene DDX58), identified as a psoriasis susceptibility gene as early as in 2012, actes as a cytoplasmic pattern recognition receptor(PRR), detect intracellular viral infection and activatea cascade of antiviral infection. Under the guidance of Wang, Zhu Huiyuan, a doctoral student, found that RIG-I was significantly increased in the mice model with psoriasis patients and psoriasis skin lesions. The specific ligand of RIG-I could directly induce the secretion of IL-23, the key inflammatory factor of psoriasis, and induce the abnormal thickening of the mouse skin. In the environment of no microorganism, IL-23 could not mediate the occurrence of psoriasis in mice, while theknock-out of gene RIG-I would significantly alleviate the symptoms of psoriasis. Therefore, the researchers put forward an idea that RNA viruses including the Influenza A virus, Newcastle Disease Virus in livestock and poultry, Respiratory Syncytial Virus and Hepatitis C Virus (HCV) may be key factors that trigger psoriasis. IL - 23, an important cytokine in the human body,has the duty of anti-microbial infections including virus, while dysregulation of antiviral response in the individuals carrying psoriasis susceptibility genes could trigger psoriasis. Wang Honglin said that if compared the human body to a car, as it is reasonable that the vehicle needed to step on the gas much morewhen climbing steep hills than when run on the flat road, it is similar that the human body would naturally increase anti-infection factors when against the virus. However,if brake pads went wrong, it was easy for the accelerated car to slow downdownhill once the ascent ended. For people with psoriatic susceptibility genes, the dysregulation of anti-viral factors would probably cause psoriasis.

Wang Honglin said, actually it had been observed that it was not common for patients with psoriasis to catch a cold, but psoriasis would be exacerbated by cold, which might be related to their abnormal activation of antiviral signaling pathway and factors; At the same time, the patients with psoriasis are prone to relapse or aggravation in autumn and winter, which may be related to the outbreak of autumn and winter influenza viruses. In addition, the high incidence of psoriasis in patients with Hepatitis Cprobablyindicates that Hepatitis C Virus maybe related to the development of psoriasis. The newly-raised hypothesis based on this study provides strong explanations for the previous clinical observations, and is believed to guide the follow-up clinical treatment of psoriasis or to promote targeted therapy for abnormal antiviral immune response.

It is reported that Wang Honglin and his group have been working on the etiology mechanism of psoriasis and its new targets as one of the most outstanding teams in the study of psoriasis in China, who have made a series of innovative achievement by the finance of the key project of National Natural Science Funds (31330026), the major research projects of National Natural Science Funds (91029730), the National Natural Science Fund Projects (31570922, 31570922) and the National Key Basic Research Program (2014 cb541905) Funding.On the one hand, they have identifedSFRP4 and pp6, the inhibitory regulators in epidermal cell proliferation, as new targets for psoriasis therapy (Jing BAI et al. J Immunol 2015; Sha YAN et al. Nat Commun 2015); On the other hand, they have revealed the new regulation mechanism of the balanceof “immunosuppression cell/immunoinduced inflammatory cells” in psoriasis (Lingyun ZHANG et al. Huaguo LI et al. J ALLERGY CLIN IMMUN 2016; Fang KE et al. Stem Cells TM 2016; Fang KE et al. Stem Cells 2014). Besides, they have obtained the 3 authorized patent. In the future, the group will continue to study the target regulation of anti-viral immune response to psoriasis.

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