Home ENGLISH MAGAZINE Psoriasis gets cellular: other than lymphocytes, tissues fall into neutrophils' NET

Psoriasis gets cellular: other than lymphocytes, tissues fall into neutrophils’ NET

Psoriasis has always been a common disease. Historically, its causes were obscure and surrounded by stigma; it wasn’t until recently that scientists categorized it as an autoimmune condition. Indeed, modern scientific research shows that the body’s own T-cells, macrophages, and dendritic cells are responsible for attacking healthy skin tissue, triggering inflammation and proliferation of skin cells, and resulting in the characteristic red, painful plaque-like lesions experienced by psoriasis patients. But although these immune-mediating cells have been identified as the primary culprits for the breakdown of healthy skin, their roles do not fully clarify the underlying cause. What makes these cells behave so abnormally? Based on their existing knowledge of the cellular and genetic pathways linked with the disease, Professor Kazumitsu Sugiura and Dr. Soichiro Watanabe from Fujita Health University, Japan, along with their colleagues, attempted to find out. Their study helped them clarify the role of another potential culprit in the formation of psoriasis lesions: white blood cells called neutrophils.

The most common type of white blood cell, neutrophils are known to be associated with various other chronic and autoimmune conditions, such as rheumatoid arthritis and lupus. Neutrophils have pro-inflammatory effects: once activated, they travel to the site of infection and effectively undergo cell death. During this process, they burst open and release their contents, forming what scientists call “neutrophil extracellular traps” (NETs), a web of proteins and genetic information from the nucleus of the former cell. NETs have reportedly been found in psoriasis lesions. However, the mechanisms linking the formation of NETs and severe skin inflammation are unknown. A precursor to the activation of NETs in psoriasis is a group of signaling proteins called IL-36 cytokines, whose role is to recruit various white blood cells and inducing inflammation. For instance, a mutation in the Il36rn gene that causes a deficiency of the IL-36 receptor antagonist (IL-36Ra), allows IL-36 to act uninhibited, leading to inflammation, inducing the proliferation of epidermal cells and increasing neutrophil count in psoriasis-like lesions in the mutant mice.

This condition is known as DITRA. This results in skin cells keratinizing (hardening) in the manner seen in psoriasis lesions. Armed with this theoretical knowledge, Prof. Sugiura and the team studied two groups of mice: one healthy (wild type) and another with the aforementioned Il36rn gene mutation. They induced psoriasis-like lesions using imiquimod, a drug known to stimulate IL-36 signaling and subsequent immunological response. After examining the lesions, they found that mutant mice suffered more severe inflammation than the wild type. A more detailed histological analysis revealed that the mutant mice also had significantly higher neutrophil counts and NET concentrations than the wild type. The scientists went one step further and examined the mRNA levels of target cytokines known to be involved in psoriasis formation to elucidate the IL-36 pathway. Having identified these cellular pathways, the scientists made a list of potential targets to block the inflammation pathway. They injected the diseased mice with Cl-amidine, a drug that specifically targets and inhibits PAD4–an enzyme responsible for the formation of NETs.

After only three days of treatment, they found the lesions, as well as the levels of inflammatory cells and IL-36 signaling proteins, significantly reduced. Although further research and human clinical trials will be required to confirm the safety and effectiveness of potential psoriasis treatments, Prof. Sugiura and his colleagues are hopeful. Dr. Soichiro Watanabe stated: “Our results suggest that IL-36Ra loss causes the development of severe psoriasis-like lesions after IMQ treatment for 3 consecutive days by increasing the infiltration of neutrophils into the skin, which is associated with the activation of IL-36R-mediated sustained inflammatory signaling. By providing mechanistic insights into the involvement of neutrophils in psoriasis pathogenesis, our study provides new directions for developing novel promising therapeutic approaches, potentially revolutionizing the quality of life of thousands of people suffering from particularly severe forms of psoriasis”.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialista in Biochimica Clinica.

Pubblicazioni scientifiche

Watanabe S et al. Sci Reports 2020; 10(1):20149.

Tsai YF et al. Antioxid Redox Signal. 2020 Dec 3.

Wójcik P et al. Int J Mol Sci. 2020 Sep; 21(18):6795. 

Wang WM, Jin HZ.J Immunol Res. 2020; 2020:3709749.

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it

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