{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen J"],"funding":["National Natural Science Foundation of China"],"pagination":["490"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12374475"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(1)"],"pubmed_abstract":["Systemic lupus erythematosus (SLE) is a complex autoimmune disease where B-cell proliferation and activation play a pivotal role in pathogenesis. While the role of basophils in SLE is recognized, the impact of basophil-derived exosomes on B-cell proliferation and activation has not been thoroughly investigated. Exosomes from human basophils in both resting and activated states were isolated and characterized. These exosomes were then co-cultured with B cells to assess their effects on B-cell survival and proliferation. To investigate the in vivo roles, a Pristane-induced lupus model in Mcpt8flox/flox CAGGCre-ERTM mice was utilized. The Pristane-Mcpt8flox/flox, CAGGCre-ERTM mice were analyzed for basophil-derived exosome accumulation in the spleen and kidneys, and the effects on immune cell proliferation and plasma cell-plasmablast balance were assessed. Transcriptomic analysis was conducted on basophil-derived exosomes to identify key non-coding RNAs. Lupus mice were humanized by transplanting peripheral blood mononuclear cells (PBMCs) from patients with SLE into immunodeficient mice to evaluate the effects of intervening miR-24550 in B cells. Activated basophil-derived exosomes were found to enhance B-cell survival and proliferation in patients with SLE. In the lupus mouse model, basophil-derived exosomes accumulated primarily in the spleen and kidneys, inducing excessive immune cell proliferation and disrupting the plasma cell-plasmablast balance, which worsened kidney damage. Transcriptomic analysis revealed key non-coding RNAs within basophil-derived exosomes. Activated basophil-derived exosomes were internalized by B cells, releasing miR-24550, which promoted B-cell proliferation. In humanized SLE mice, inhibiting miR-24550 in B cells reduced immune hyperactivation and improved renal function, similar to the effects of inhibiting basophil-derived exosomes release in Pristane-Mcpt8flox/flox, CAGGCre-ERTM mice. Ultimately, basophil-derived exosomal miR-24550 promotes B-cell proliferation and activation by targeting Krüppel-like factor 5 (KLF5), which exacerbates SLE progression. Basophil-derived exosomal miR-24550 promotes B-cell proliferation and activation by targeting KLF5, thereby exacerbating SLE progression. This study presents a novel strategy for SLE prevention and treatment."],"journal":["BMC medicine"],"pubmed_title":["Basophil-derived exosomes exacerbate systemic lupus erythematosus by regulating B-cell proliferation via miR-24550."],"pmcid":["PMC12374475"],"funding_grant_id":["No. 82070757, 82270770"],"pubmed_authors":["Yang L","Chen J","Lu X","Lun J","Liu HF","Liu X","You L","Guo F","Xiao H","Liao S","Pan Q","Xu X","Huang B"],"additional_accession":[]},"is_claimable":false,"name":"Basophil-derived exosomes exacerbate systemic lupus erythematosus by regulating B-cell proliferation via miR-24550.","description":"Systemic lupus erythematosus (SLE) is a complex autoimmune disease where B-cell proliferation and activation play a pivotal role in pathogenesis. While the role of basophils in SLE is recognized, the impact of basophil-derived exosomes on B-cell proliferation and activation has not been thoroughly investigated. Exosomes from human basophils in both resting and activated states were isolated and characterized. These exosomes were then co-cultured with B cells to assess their effects on B-cell survival and proliferation. To investigate the in vivo roles, a Pristane-induced lupus model in Mcpt8flox/flox CAGGCre-ERTM mice was utilized. The Pristane-Mcpt8flox/flox, CAGGCre-ERTM mice were analyzed for basophil-derived exosome accumulation in the spleen and kidneys, and the effects on immune cell proliferation and plasma cell-plasmablast balance were assessed. Transcriptomic analysis was conducted on basophil-derived exosomes to identify key non-coding RNAs. Lupus mice were humanized by transplanting peripheral blood mononuclear cells (PBMCs) from patients with SLE into immunodeficient mice to evaluate the effects of intervening miR-24550 in B cells. Activated basophil-derived exosomes were found to enhance B-cell survival and proliferation in patients with SLE. In the lupus mouse model, basophil-derived exosomes accumulated primarily in the spleen and kidneys, inducing excessive immune cell proliferation and disrupting the plasma cell-plasmablast balance, which worsened kidney damage. Transcriptomic analysis revealed key non-coding RNAs within basophil-derived exosomes. Activated basophil-derived exosomes were internalized by B cells, releasing miR-24550, which promoted B-cell proliferation. In humanized SLE mice, inhibiting miR-24550 in B cells reduced immune hyperactivation and improved renal function, similar to the effects of inhibiting basophil-derived exosomes release in Pristane-Mcpt8flox/flox, CAGGCre-ERTM mice. Ultimately, basophil-derived exosomal miR-24550 promotes B-cell proliferation and activation by targeting Krüppel-like factor 5 (KLF5), which exacerbates SLE progression. Basophil-derived exosomal miR-24550 promotes B-cell proliferation and activation by targeting KLF5, thereby exacerbating SLE progression. This study presents a novel strategy for SLE prevention and treatment.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-09T10:36:52.221Z","creation":"2026-04-08T00:48:17.529Z"},"accession":"S-EPMC12374475","cross_references":{"pubmed":["40846943"],"doi":["10.1186/s12916-025-04324-3"]}}