Investigating the mechanisms contributing to impaired regulatory function of B cells in autoimmunity
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
The implementation of biological therapies has significantly advanced the management of autoimmune diseases (AIDs). However, the failure to achieve clinical remission in 'non-responders' remains a significant and unmet challenge. B cells are central to the immunopathogenesis of AIDs. Alterations in B cell phenotype and function have been described in several AIDs, with one key feature being the dysregulation of the regulatory B cell compartment.
Regulatory B cells (Bregs) modulate immune responses via several mechanisms, although primarily via the secretion of IL-10. Their importance in the maintenance of immune homeostasis has been highlighted not only in AIDs but also in other immune-mediated pathologies, including cancers and chronic infections. In the context of AIDs, numerical or/ and functional abnormalities in Bregs have been described across several diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS), and found to be associated with disease severity1. Importantly, the ability of B cells to secrete IL-10 has also been associated with treatment response.
Despite a continuous effort towards understanding Breg biology, identity and function in healthy individuals, the mechanisms promoting loss of Breg function in AIDs remain unknown. The goal of this project is to uncover the signals driving the loss of human Breg function in AIDs (SLE and RA), and to develop disease relevant in vitro "loss of function" culture systems that would provide new opportunities to develop and test B cell-targeted therapies.
The project, using blood samples from healthy controls/ patients, will involve several cutting-edge techniques, including single-cell transcriptomics and proteomics, in addition to flow cytometry, mass spectrometry, LegendPlex bead-based immunoassays and complex in vitro cell culture assays. The student will also gain interdisciplinary skills in bioinformatics and complex disease aetiology.
Regulatory B cells (Bregs) modulate immune responses via several mechanisms, although primarily via the secretion of IL-10. Their importance in the maintenance of immune homeostasis has been highlighted not only in AIDs but also in other immune-mediated pathologies, including cancers and chronic infections. In the context of AIDs, numerical or/ and functional abnormalities in Bregs have been described across several diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS), and found to be associated with disease severity1. Importantly, the ability of B cells to secrete IL-10 has also been associated with treatment response.
Despite a continuous effort towards understanding Breg biology, identity and function in healthy individuals, the mechanisms promoting loss of Breg function in AIDs remain unknown. The goal of this project is to uncover the signals driving the loss of human Breg function in AIDs (SLE and RA), and to develop disease relevant in vitro "loss of function" culture systems that would provide new opportunities to develop and test B cell-targeted therapies.
The project, using blood samples from healthy controls/ patients, will involve several cutting-edge techniques, including single-cell transcriptomics and proteomics, in addition to flow cytometry, mass spectrometry, LegendPlex bead-based immunoassays and complex in vitro cell culture assays. The student will also gain interdisciplinary skills in bioinformatics and complex disease aetiology.
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/W007428/1 | 30/09/2022 | 29/09/2028 | |||
2930346 | Studentship | MR/W007428/1 | 30/09/2024 | 29/09/2028 | Rebecca Rowan |