Sci Rep: The immunological mechanism by which psoriasis occurs

December 5, 2019 // -- More than 130 million people worldwide suffer from common psoriasis, a chronic disease characterized by inflamed skin, scales and dry patches.
, the pathology is not entirely clear.
a recent study, dermatology researchers at Fujita Health University found complex cellular mechanisms that cause psoriasis attacks and highlighted potential therapeutic targets for future treatments.
psoriasis has always been a common disease.
until recently that scientists classified it as an autoimmune disease.
Modern scientific studies have shown that the body's own T-cells, macrophages, and degenerative cells attack healthy skin tissue, trigger inflammation and proliferation of skin cells, and cause psoriasis patients to experience typical red, painful plaque-like lesions.
(Photo Source: www.pixabay.com) But while these immuno-mediated cells have been identified as the main culprits for damaging healthy skin, their role does not fully understand the root cause.
what makes these cells behave abnormally? Professor Kazumitsu Sugiura and Dr Soichiro Watanabe and their colleagues are trying to find out based on their existing knowledge of disease-related cells and genetic pathways.
their research has revealed another potential culprit: neutral granulocytes.
their findings were published in the journal Scientific Reports.
nexus is the most common type of white blood cell and is associated with a variety of other chronic and autoimmune diseases such as rheumatoid arthritis and lupus.
non-neutral granulocytes have an inflammatory effect: once activated, they reach the infected site and effectively cause cell death.
in the process, they suddenly open and release their inclusions, forming what scientists call a neutride white blood cell trap (NETs), a cluster of proteins and DNA from the nucleus.
reported that NET was found in psoriasis lesions.
, however, the mechanisms that link the formation of NETs to severe skin inflammation are unclear.
Sugiura explains: "NET and neugenic granulocytes can induce inflammation through a variety of mechanisms; we aim to clarify the role of NET signaling and possibly prevent the occurrence of severe psoriasis-like lesions.
" NETs activation in psoriasis is a precursor to IL-36, which is well known for its role in raising various white blood cells and inducing inflammation.
For example, a mutation in the Il36rn gene that causes the loss of the IL-36 subject antagonist (IL-36Ra) protein can make IL-36 function unsuppressed, leading to inflammation, inducing the proliferation of supersectal cells and increasing the count of neutrophils.
psoriasis-like lesions in mutant mice in a condition called DITRA.
this causes skin cells to hornize in the way seen in psoriasis lesions.
Sugiura and his team developed these theories and studied two groups of mice: one group of healthy (wild) mice and the other with the above-mentioned Il36rn gene mutation.
they induced psoriasis-like lesions using Mimimot, a drug known to stimulate IL-36 signaling and subsequent immune responses.
examined the lesions, they found that mutant mice suffered more severe inflammation than wild mice.
more in-depth histological analysis showed that the neutral granulocyte count and NET concentration of mutant mice were also significantly higher than in the wild.
scientists took another step forward by studying the mRNA levels of target cytokines known to be associated with psoriasis formation to clarify the IL-36 pathway, thus establishing a causal link.
these complex cellular mechanisms, the scientists listed potential targets for blocking inflammatory pathways and preventing psoriasis.
they injected the sick mice with Cl-am, a specific drug that targets and inhibits PAD4, the enzyme responsible for forming NET.
three days of treatment, they found significantly lower levels of lesions as well as inflammatory cells and IL-36 signaling proteins.
although further research and human clinical trials are needed to confirm the safety and effectiveity of potential psoriasis treatments, Professor Sugiura and his colleagues are hopeful.
Soichiro Watanabe said: "By providing insights into the pathogenesis of neugenic granulocytes involved in psoriasis, our research provides a new direction for the development of novel and promising treatments that could change the quality of life of thousands of people with particularly severe psoriasis.
() Source: What makes psoriasis sore: Novel of the immune system in the original origin of the disease: Soichiro Watanabe et al, Neutrophil extracellular traps are induced in a psoriasis model of model interleukin-36 receptor antagonist-deficient mice, Scientific Reports (2020). DOI: 10.1038/s41598-020-76864-y。