biostudies-literatureLiu WNHLBI NIH HHSNCI NIH HHS572-586https://www.ebi.ac.uk/biostudies/studies/S-EPMC10399458biostudies-literatureUnknown2(6)Clonal hematopoiesis (CH) increases the risk of atherosclerotic cardiovascular disease possibly due to increased plaque inflammation. Human studies suggest that limitation of interleukin-6 (IL-6) signaling could be beneficial in people with large CH clones, particularly in <i>TET2</i> CH. Here we show that IL-6 receptor antibody treatment reverses the atherosclerosis promoted by <i>Tet2</i> CH, with reduction of monocytosis, lesional macrophage burden and macrophage colony-stimulating factor 1 receptor (CSF1R) expression. IL-6 induces expression of <i>Csf1r</i> in <i>Tet2</i>-deficient macrophages through enhanced STAT3 binding to its promoter. In mouse and human <i>Tet2</i>-deficient macrophages, IL-6 increases CSF1R expression and enhances macrophage survival. Treatment with the CSF1R inNature cardiovascular researchBlockade of IL-6 signaling alleviates atherosclerosis in <i>Tet2</i>-deficient clonal hematopoiesis.PMC10399458R01 HL148071R01 HL118567R01 HL163099P30 CA008748R01 HL155431R01 HL134892R35 HL145228Yalcinkaya MOlszewska MPapapetrou EPXiao TAmpomah PBLiu WVela PSLevine RWang NTall ARTabas IWang RLibby PMaestre IFHeimlich JBBick AGfalseBlockade of IL-6 signaling alleviates atherosclerosis in <i>Tet2</i>-deficient clonal hematopoiesis.Clonal hematopoiesis (CH) increases the risk of atherosclerotic cardiovascular disease possibly due to increased plaque inflammation. Human studies suggest that limitation of interleukin-6 (IL-6) signaling could be beneficial in people with large CH clones, particularly in <i>TET2</i> CH. Here we show that IL-6 receptor antibody treatment reverses the atherosclerosis promoted by <i>Tet2</i> CH, with reduction of monocytosis, lesional macrophage burden and macrophage colony-stimulating factor 1 receptor (CSF1R) expression. IL-6 induces expression of <i>Csf1r</i> in <i>Tet2</i>-deficient macrophages through enhanced STAT3 binding to its promoter. In mouse and human <i>Tet2</i>-deficient macrophages, IL-6 increases CSF1R expression and enhances macrophage survival. Treatment with the CSF1R in2023-01-01T00:00:00Z2023 Jun2025-04-04T07:44:56.418Z2025-04-04T07:44:56.418ZS-EPMC103994583753907710.1038/s44161-023-00281-3