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Tick cysteine protease inhibitors suppress immune responses in mannan-induced psoriasis-like inflammation
The Eighth People’s Hospital of Guangzhou, Guangzhou, China; Southern Medical University, Guangzhou, China.
Institute of Parasitology, České Budějovice, Czech Republic.ORCID iD: 0000-0002-9978-3409
Southern Medical University, Guangzhou, China.
Southern Medical University, Guangzhou, China.
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2024 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 15, article id 1344878Article in journal (Refereed) Published
Abstract [en]

Protease inhibitors regulate various biological processes and prevent host tissue/organ damage. Specific inhibition/regulation of proteases is clinically valuable for treating several diseases. Psoriasis affects the skin in the limbs and scalp of the body, and the contribution of cysteine and serine proteases to the development of skin inflammation is well documented. Cysteine protease inhibitors from ticks have high specificity, selectivity, and affinity to their target proteases and are efficient immunomodulators. However, their potential therapeutic effect on psoriasis pathogenesis remains to be determined. Therefore, we tested four tick cystatins (Sialostatin L, Sialostatin L2, Iristatin, and Mialostatin) in the recently developed, innate immunity-dependent mannan-induced psoriasis model. We explored the effects of protease inhibitors on clinical symptoms and histological features. In addition, the number and percentage of immune cells (dendritic cells, neutrophils, macrophages, and γδT cells) by flow cytometry, immunofluorescence/immunohistochemistry and, the expression of pro-inflammatory cytokines (TNF-a, IL-6, IL-22, IL-23, and IL-17 family) by qPCR were analyzed using skin, spleen, and lymph node samples. Tick protease inhibitors have significantly decreased psoriasis symptoms and disease manifestations but had differential effects on inflammatory responses and immune cell populations, suggesting different modes of action of these inhibitors on psoriasis-like inflammation. Thus, our study demonstrates, for the first time, the usefulness of tick-derived protease inhibitors for treating skin inflammation in patients. Copyright © 2024 Wu, Jmel, Chai, Tian, Xu, Hui, Nandakumar and Kotsyfakis.

Place, publisher, year, edition, pages
Lausanne: Frontiers Media S.A., 2024. Vol. 15, article id 1344878
Keywords [en]
autoimmune disease, immune responses, protease inhibitors, psoriasis, tick
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:hh:diva-52959DOI: 10.3389/fimmu.2024.1344878ISI: 001175852300001PubMedID: 38444844Scopus ID: 2-s2.0-85186632795OAI: oai:DiVA.org:hh-52959DiVA, id: diva2:1847683
Note

Funding: “High-level talent introduction plan” project grants from Southern Medical University, Guangzhou, China (Grant numbers C1034211, C1051004) given to KN, the Project of Innovative Talent Exchange Foreign Experts under “The Belt and Road” (DL2023030011L) and Guangdong Basic and Applied Basic Research Foundation (2023A1515010914) given to XX. MK received funding received from the Grant Agency of the Czech Republic (grant 19-38207247S) and ERD Funds, project CePaVip OPVVV (No. 384 CZ.02.1.01/0.0/0.0/16_019/0000759). MJ received the European Union funding (MSCA fellowship CZ) within the Operational program Jan Amos Komensky (OP JAK), Priority Research and development (Project No. CZ.02.01.01/00/22_010/0003414).

Available from: 2024-03-28 Created: 2024-03-28 Last updated: 2024-03-28Bibliographically approved

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Nandakumar, Kutty Selva

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