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Plasmablasts, including an IL\u201010\u2013producing regulatory subset, expand during sepsis to exert immunosuppressive functions. This study examined how depleting plasmablasts can improve the prognosis of sepsis, and investigated the underlying mechanisms by focusing on neutrophil function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Plasmablasts were depleted in vivo in CD138\u2010diphtheria toxin receptor (DTR) transgenic mice subjected to caecal ligation and puncture (CLP)\u2010induced sepsis. The effects of plasmablast depletion on animal survival, bacterial load, inflammatory mediators, and neutrophil number and function were assessed. The proteasome inhibitor bortezomib (BTZ) was evaluated for its ability to suppress plasmablasts, and its therapeutic efficacy in wild\u2010type mice with sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Plasmablast depletion in CD138\u2010DTR mice was associated with an increase in the number and antibacterial function of neutrophils, including increased production of reactive oxygen species (ROS) and phagocytic capacity. In vitro co\u2010culture experiments demonstrated that plasmablasts suppressed neutrophil activity, an effect mediated by adenosine and IL\u201010 signalling. Treatment of wildtype septic mice with BTZ effectively reduced plasmablast abundance and CD39 expression. BTZ 0.05\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      mirrored the protective effects of genetic ablation, improved survival, reduced bacterial burden and inflammation and improved neutrophil\u2010mediated bacterial clearance. At high concentrations, BTZ worsened outcomes and is an unlikely magic bullet for sepsis without stringent dosing controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Plasmablasts contribute to sepsis immunosuppression by affecting neutrophil function. The clinically\u2010available drug bortezomib can target this population, positioning plasmablast inhibition as a novel and translatable therapeutic strategy to improve bacterial clearance and survival in sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70450","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:42:56Z","timestamp":1776775376000},"page":"3849-3865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bortezomib promotes neutrophil\u2010mediated bacterial clearance in sepsis by inhibiting plasmablast activation"],"prefix":"10.1111","volume":"183","author":[{"given":"Wang","family":"Jianyao","sequence":"first","affiliation":[{"name":"Department of General Surgery Tianjin Medical University General Hospital  Tianjin China"},{"name":"Unit of Infection and Immunity, Tianjin Medical University General Hospital Institute of General Surgery  Tianjin 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