2020 Fiscal Year Final Research Report
Elucidation of pathomechanisms of deficiency of interleukin-36 receptor antagonist to develop innovative therapies for the disease
| Project/Area Number |
18K08281
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53050:Dermatology-related
|
|---|
| Research Institution | Fujita Health University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | IL-36受容体拮抗因子欠損症 / IL36RN / 膿疱性乾癬 / 好中球細胞外トラップ / ノックアウトマウス / 接触皮膚炎 / 創傷治癒 / TLR4 |
|---|
| Outline of Final Research Achievements |
The principal investigators found that the majority of the etiology of the designated intractable pustular psoriasis (generalized) (GPP) was IL-36 receptor antagonist (IL-36Ra) deficiency (DITRA). We investigate the pathophysiology of various skin disorders in DITRA. The purpose of this studies are follows; (1) to analyzed therapeutic effect of DITRA of neutrophil extracellular traps (NETs) inhibitors on GPP model (2) to elulcidate pathophysiology of exacerbation of contact dermatitis due to IL-36Ra deficiency (3) to elucidate pathphysiology of prolong the healing of skin ulcers due to IL-36Ra deficiency. As a result of the research, NETs have been shown to be new therapeutic targets in DITRA. It was revealed that IL-36Ra deficiency can be an exacerbating factor for contact dermatitis and wound healing. Furthermore, it was suggested that inhibition of TLR4 signal by TAK-242 may be a new therapeutic agent for contact dermatitis and wound healing.
|
| Free Research Field |
皮膚科学
|
| Academic Significance and Societal Importance of the Research Achievements |
IL-36Ra欠損症のGPP様の皮疹ではNETｓが亢進していることを証明し、GPPの新たな知見を提供した。さらに、NETsはDITRAにおいて新たな治療標的となることを提示した。さらに、IL-36Ra欠損が、好中球炎症を引き起こし、接触性皮膚炎と創傷治癒を増悪させることを示した。TAK-242によるTLR4シグナルの阻害が接触皮膚炎と創傷治癒の新たな治療薬となる可能性を示唆した。
|
