ROLE OF ANNEXIN A1 AND ITS MIMETIC PEPTIDE IN A MURINE MODEL OF IMIQUIMODE-INDUCED PSORIASIS

• Grant number: 26/03831-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2026
• End date: April 30, 2031
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Nathália Rodrigues da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation, leukocyte infiltration, and exacerbated production of pro-inflammatory cytokines, particularly the IL-23/IL-17 axis. Annexin A1 (AnxA1) is an anti-inflammatory protein involved in modulating the immune response and resolving inflammation; however, its role in the pathophysiology of psoriasis and its therapeutic potential are not yet fully understood. This project aims to investigate the role of endogenous AnxA1 in the pathogenesis of imiquimod (IMQ)-induced psoriasis, as well as the therapeutic effects of transdermal microneedling treatment containing the mimetic peptide Ac2-26, using wild-type (WT) and AnxA1 knockout mice (AnxA1¿/¿). Experimental psoriasis will be induced by topical application of IMQ to the backs of animals, with transdermal treatment on days 4 and 6 of the protocol. The severity of skin lesions will be assessed by clinical score (PASI), skin thickness, and histopathological analyses. The cutaneous inflammatory infiltrate will be characterized by immunohistochemistry to identify dendritic cells, macrophages, T lymphocytes, and mast cells. The systemic inflammatory response will be evaluated through morphological and weight changes in the spleen, as well as by immunophenotyping of leukocyte populations using flow cytometry. Additionally, the profile of inflammatory cytokines in the skin and plasma will be determined by multiplex assay, and the expression of AnxA1 and FPR1 and FPR2 receptors will be evaluated in the skin by Western blotting. Taken together, the results will contribute to advancing knowledge about the role of AnxA1 and the AnxA1/FPRs axis in modulating cutaneous inflammation, as well as exploring the therapeutic potential of the Ac2-26 peptide in the context of psoriasis. (AU)