Project R-17024

Transcriptional and metabolic drivers of the double negative (DN) B cell subset 1 in multiple sclerosis: new targets for neuroinflammation (Research)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). B cells are important contributors to MS pathology by producing antibodies that target self-antigens, stimulating T cell responses, and secreting cytokines that shape inflammatory responses. Our research group recently showed that IgD⁻CD27⁻ double negative (DN) B cells are increased in the peripheral blood and cerebrospinal fluid of MS patients. These cells display pro-inflammatory and disease-associated functional characteristics, suggesting that they may actively contribute to ongoing CNS inflammation. This project aims to elucidate the molecular mechanisms that regulate DN1 cell function and metabolic activity in MS, since preliminary data indicate that the DN1 subtype is the predominant DN population in the disease. Ex vivo, in vitro, and in vivo experiments will be used to investigate genes and proteins that are differentially expressed in DN1 cells and linked to their activation and metabolism. This project will increase insight into the biological pathways underlying the involvement of DN1 cells in MS pathology. In the future, the identification of novel B-cell-related targets can lead to more personalized, targeted therapy for MS.

01 November 2026 - 31 October 2030