AGE-ASSOCIATED CLONAL HEMATOPOIESIS ACCELERATES CARDIO-METABOLIC DISEASE DEVELOPMENT

摘要

As demonstrated herein, a preferential and progressive expansion of a subset of hematopoietic cells bearing somatic mutations in TET2 leads to pro-inflammatory IL-1β signaling at multiple levels, including increased IL-1β transcription, increased NLRP3 inflammasome-mediated IL-1β secretion, and increased IL-1-Receptor 1-mediated IL-1β signaling. Accordingly, provided herein are compositions, methods, and assays for modulating TET2 mutation-mediated IL-1β (interleukin-1β) proinflammatory activity, particularly when caused by somatic mutations in TET2.