Analysis of Oral Tolerance with Collagen V Peptides on Pulmonary Fibrosis in a Murine Model of Systemic Sclerosis

• Grant number: 25/02751-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Ana Paula Pereira Velosa
• Grantee: Gabriele Dall Agnol
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Systemic Sclerosis (SS) is a chronic disease characterized by a fibrotic process, preceded by autoimmune changes and vasculopathy; however, its etiology is still not fully understood. Annually, around 14 new cases of SS per million inhabitants are reported worldwide, two-thirds of which present with lung diseases, and 20-30% develop progressive interstitial lung disease. In the early stages of the disease, studies show an increase in the frequency of anti-collagen V antibodies in the serum of patients. These data highlight collagen V (Col.V) due to its immunogenic properties, antigenic properties, and potential to become an autoantigen when exposed to agents inducing chronic endothelial injury. This study aims to evaluate the effect of oral tolerance induction to the ¿1(V) chain and the Col5A1(1.049) and Col5A1(1.439) peptides of the ¿1(V) chain on lung remodeling in a mouse model of SS induced by immunization with Col V. The analysis will involve immunolocalization and quantification of collagen types I, III, and V, through image analysis, with total collagen quantification performed by measuring 4-hydroxyproline. Subsequently, the data obtained will be analyzed using statistical tests for comparison. In this context, the importance of the study is emphasized, as pulmonary involvement is the leading cause of morbidity and mortality in SS, which has a high prevalence and significant social cost, in addition to limited therapeutic options. Thus, mucosal tolerance may offer an adjunctive therapeutic alternative in the treatment of the disease.