Exploring the Role of Endogenous Retroviruses in Atopic Dermatitis

• Grant number: 25/15738-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2026
• End date: January 31, 2031
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Djalma de Souza Lima Júnior
• Grantee: Fernanda de Sousa Colombini
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/09270-2 - Decoding the role of endogenous retroviruses in controlling type 2 immunity., AP.JP

Abstract

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by intense pruritus (itching), erythema (redness), and epidermal barrier dysfunction. It affects individuals of all ages, but its onset is typically observed during early childhood. AD is a complex multifactorial condition influenced by a combination of genetic, environmental, and immunological factors. Despite its high prevalence and impact on the quality of life of affected individuals, the exact etiology of AD remains incompletely understood.Recent advances in research have revealed the potential involvement of endogenous retroviruses (ERVs) in the pathogenesis of various diseases, including autoimmune and inflammatory disorders. ERVs are remnants of ancient retroviral infections that have integrated into the genome of the host organism. These viral elements, once considered "junk DNA," have emerged as important regulators of gene expression and immune responses. The expression and activation of ERVs have been implicated in several human diseases, with evidence suggesting their association with inflammation, autoimmunity, and cancer. Recently, we found that the skin microbiota promotes a discrete expression of defined endogenous retroviruses which are critical for homeostatic immunity to the microbiota in skin tissue. The identification of ERVs in the context of AD has sparked interest in understanding their potential role in disease development and progression. ERVs have the ability to influence gene expression patterns and cellular functions by modulating immune responses and epigenetic regulation. Furthermore, ERVs possess immunostimulatory properties and can activate innate immune pathways, triggering the release of pro-inflammatory cytokines and chemokines. These events can contribute to the chronic inflammation observed in AD.In addition to the involvement of ERVs, dietary factors have also been recognized as potential contributors to the pathogenesis of AD. A high-fat diet (HFD) has been linked to increased systemic inflammation and altered immune responses. Interestingly, we have found that systemic inflammation induced by high-fat diet promoted enhanced ERV expression and an aberrant skin inflammatory responses to the microbiota, indicating that the intensity and quality of skin immune responses to the microbiota under inflammatory settings are controlled by the expression of ERVs. The influence of HFD on the skin, particularly in the context of AD, remains largely unexplored. Understanding the interaction between ERVs, HFD, and AD could provide valuable insights into the underlying mechanisms of disease pathogenesis and identify potential targets for therapeutic interventions.Therefore, this research project aims to investigate the role of endogenous retroviruses in AD pathogenesis under steady state and inflammatory (high-fat diet feeding) conditions. By characterizing the expression profiles of ERVs in AD at steady state and in a context of obesity and elucidating the impact of ERV expression, host metabolic changes, and associated immune responses, we seek to unravel the complex interplay between these factors in the context of AD. The findings of this study may pave the way for the development of novel therapeutic strategies and dietary interventions targeting ERVs and HFD in the prevention and management of atopic dermatitis. (AU)