CD19-targeting chimeric antigen receptor (CAR) T cells protect from anti-neutrophil cytoplasmic autoantibody (ANCA)-induced acute kidney injury. This study investigated the efficacy of CD19 CAR T cells in a preclinical model of ANCA-associated vasculitis (AAV), specifically in mice with anti-myeloperoxidase (MPO)-induced glomerulonephritis (NCGN). The hypothesis was that CD19 CAR T cells would deplete B cells, including those producing MPO-ANCA, thereby protecting against NCGN. CD19 CAR T cells were constructed with an extracellular antibody-derived antigen-binding domain, a transmembrane domain, an intracellular signaling domain, and a costimulatory domain. These CAR T cells were tested in a murine model where MPO gene-deficient mice were immunized with murine MPO to induce anti-MPO antibodies. After irradiation and bone marrow transplantation, mice were reconstituted with either CD19 CAR T cells or control SP6 CAR T cells. CD19 CAR T cells efficiently migrated to and persisted in bone marrow, spleen, peripheral blood, and kidneys for up to 8 weeks. They depleted B cells and plasmablasts, enhanced the decline of MPO-ANCA, and protected mice from NCGN. The study demonstrated that CD19 CAR T cells effectively depleted B cells and plasmablasts, leading to a significant reduction in kidney damage and protection from NCGN. This suggests that CD19 CAR T cells could be a novel treatment strategy for patients with ANCA-vasculitis, potentially leading to drug-free remission. The findings highlight the potential of CAR T cell therapy in autoimmune diseases, offering a promising alternative to traditional B cell-depleting therapies like rituximab. However, further research is needed to evaluate long-term safety and efficacy in human patients.CD19-targeting chimeric antigen receptor (CAR) T cells protect from anti-neutrophil cytoplasmic autoantibody (ANCA)-induced acute kidney injury. This study investigated the efficacy of CD19 CAR T cells in a preclinical model of ANCA-associated vasculitis (AAV), specifically in mice with anti-myeloperoxidase (MPO)-induced glomerulonephritis (NCGN). The hypothesis was that CD19 CAR T cells would deplete B cells, including those producing MPO-ANCA, thereby protecting against NCGN. CD19 CAR T cells were constructed with an extracellular antibody-derived antigen-binding domain, a transmembrane domain, an intracellular signaling domain, and a costimulatory domain. These CAR T cells were tested in a murine model where MPO gene-deficient mice were immunized with murine MPO to induce anti-MPO antibodies. After irradiation and bone marrow transplantation, mice were reconstituted with either CD19 CAR T cells or control SP6 CAR T cells. CD19 CAR T cells efficiently migrated to and persisted in bone marrow, spleen, peripheral blood, and kidneys for up to 8 weeks. They depleted B cells and plasmablasts, enhanced the decline of MPO-ANCA, and protected mice from NCGN. The study demonstrated that CD19 CAR T cells effectively depleted B cells and plasmablasts, leading to a significant reduction in kidney damage and protection from NCGN. This suggests that CD19 CAR T cells could be a novel treatment strategy for patients with ANCA-vasculitis, potentially leading to drug-free remission. The findings highlight the potential of CAR T cell therapy in autoimmune diseases, offering a promising alternative to traditional B cell-depleting therapies like rituximab. However, further research is needed to evaluate long-term safety and efficacy in human patients.