Elucidation of Cellular and Molecular Mechanisms in the Immunopathogenesis of Allergic Inflammatory Diseases Using Spatial and Single-Cell Sequencing Techniques

• Grant number: 24/18498-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: May 31, 2029
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Helder Takashi Imoto Nakaya
• Grantee: Guilherme Rodrigues de Mira
• Host Institution: Centro de Inovação da USP (INOVA). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Allergic diseases represent one of the most common groups of inflammatory pathologies worldwide, with significant impacts on human health and the global economy. The allergic march is classically described as a temporal allergic progression, in which 1 out of 3 individuals affected by atopic dermatitis (AD) develop allergic asthma (AA) over their lifetime. Although the prevalence of AA in patients with AD is well established, the immunological mechanisms involved in the immunopathogenesis of the allergic march progression remain unknown, even though both pathologies are mediated by Th2-characteristic inflammation-marked mainly by eosinophilic infiltration, Th2 cell recruitment, production of cytokines such as IL-4, IL-5, and IL-13, and IgE production. In the literature, two distinct hypotheses are proposed to explain the pathogenesis of the association between AD and AA: intrinsic dysfunctional characteristics of the epithelial barrier lead to the development of AD followed by AA; or a polarized inflammatory response in individuals induces the pathogenesis of the allergic march, which together highlights a gap in the understanding of the immunopathological processes of the allergic march. Given the heterogeneity and complexity of these allergic inflammatory conditions, integrated omics data approaches may advance the understanding of the cellular and molecular immunological mechanisms involved, such as the use of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST). Therefore, the objective of this project is to elucidate the common and distinct immunological mechanisms between the pathologies of the allergic march (AD/AA) at the transcriptional and spatial levels in an integrated manner, seeking to understand the still poorly understood cellular and molecular interaction networks and pathways in AD and AA. (AU)