Establishment of the molecular basis of new therapies for intractable itch and pathology in psoriasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K16353
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Juntendo University
• Principal Investigator: Komiya Eriko 順天堂大学, 医学(系)研究科(研究院), 特任助教 (90647009)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 乾癬 / かゆみ / 神経ペプチド / CD26

Outline of Final Research Achievements

CD26 is a multifunctional protein with dipeptidyl peptidase IV (DPPIV) enzyme activity and is highly expressed in the sera of psoriasis patients. When we established psoriasis models, CD26 transgenic mice displayed exacerbation of the number of scratching behavior, and psoriatic pathology, compared with wildtype. Therefore, we aimed to develop a new treatment for psoriasis that acts on both itch and pathology by targeting the CD26 molecule.
The results obtained showed that CD26 exacerbated itch by its DPPIV enzyme activity, thorough the degradation of substance-P (SP), which is a member of neuropeptides. In contrast to the preliminary experiment,CD26 itself did not exacerbate the pathology, we identified interleukin 26 (IL-26), which is induced by CD26, exacerbated psoriatic pathology by its angiogenesis activity.

Free Research Field

かゆみ

Academic Significance and Societal Importance of the Research Achievements

かゆみは、乾癬の患者さんの約6-9割が経験し、乾癬の症状の中でももっともつらいものうちの1つである。また、乾癬のかゆみには既存の抗ヒスタミン薬に対し、効果を示さないものが多く存在しており、その治療法の開発は急務であると言える。今回の結果は、乾癬のかゆみの増悪メカニズムの一端を明らかにしたのと同時に、CD26が発現促進しているIL-26の乾癬における紅斑(血管新生)促進メカニズムについても明らかにし、抗IL-26抗体が乾癬症状を抑えることも実験モデルで示した。
これらの結果を組み合わせることで、乾癬の病状とかゆみに対して効果的な新規治療法を確立できる可能性が示された。