{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li R"],"funding":["Biogen","the Melissa and Paul Anderson Gift Fund at the University of Pennsylvania","NIAID NIH HHS","Center for Mitochondrial and Epigenomic Medicine"],"pagination":["505-521"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8960592"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["143(4)"],"pubmed_abstract":["Inhibition of Bruton's Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little is known; however, about how BTKi influences MS disease-implicated functions of B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, BTKi attenuates B-cell:T-cell interactions via a novel mechanism involving modulation of B-cell metabolic pathways which, in turn, mediates an anti-inflammatory modulation of the B cells. In vitro, BTKi, as well as direct inhibition of B-cell mitochondrial respiration (but not glycolysis), limit the B-cell capacity to serve as APC to T cells. The role of metabolism in the regulation of human B-cell responses is confirmed when exa"],"journal":["Acta neuropathologica"],"pubmed_title":["BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy."],"pmcid":["PMC8960592"],"funding_grant_id":["UM1 AI144288"],"pubmed_authors":["Romberg N","Burns JC","Hopkins BT","Le Coz C","Goldstein AC","Li R","Banwell BL","Bar-Or A","Tang H","Mingueneau M","Luning Prak ET","Zhang B","de Barcelos IP"],"additional_accession":[]},"is_claimable":false,"name":"BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy.","description":"Inhibition of Bruton's Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little is known; however, about how BTKi influences MS disease-implicated functions of B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, BTKi attenuates B-cell:T-cell interactions via a novel mechanism involving modulation of B-cell metabolic pathways which, in turn, mediates an anti-inflammatory modulation of the B cells. In vitro, BTKi, as well as direct inhibition of B-cell mitochondrial respiration (but not glycolysis), limit the B-cell capacity to serve as APC to T cells. The role of metabolism in the regulation of human B-cell responses is confirmed when exa","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-31T03:14:45.752Z","creation":"2024-11-05T18:22:23.173Z"},"accession":"S-EPMC8960592","cross_references":{"pubmed":["35303161"],"doi":["10.1007/s00401-022-02411-w"]}}