Addressing a gut-skin axis that underlies a common mechanism associated with the immunopathogenesis of Crohn’s disease and Hidradenitis Suppurativa

• Autor(a) principal: Nogueira, Rafaela Sousa
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/162096
• topic: Autoimmunity; Glycosylation; Gut-Skin axis; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder and one of the extraintestinal manifestations of Crohn’s disease (CD). Although the association between both is not yet clarified, previous studies demonstrated a shared accumulation of anti-glycan antibodies, which raises relevant questions about a potential common immunopathogenesis of both inflammatory diseases, that we herein propose to tackle. Glycans are complex and diverse structures decorating the cell surface and mediating a wide range of cellular and biological mechanisms. The glycome of each cell is unique, and the information it contains can be decoded by the immune system, which highlights glycans as major molecules in homeostatic and pathological conditions. In this project, we revealed that HS and CD patients display a common abnormal glycosignature, together with high titters of antibodies against these structures. Interestingly, we also demonstrated that these antibodies may mediate common pathogenic mechanisms, important for the establishment of a gut-skin inflammatory axis. Finally, our results were confirmed in vivo, using a glycoengineered mouse model susceptible to colitis.