| The transcription factor ZEB2 drives the formation of age-associated B cells | |
| 論文作者 | Dai, D; Gu, SS; Han, XX; Ding, HH; Jiang, Y; Zhang, XO; Yao, C; Hong, SM; Zhang, JS; Shen, YW; Hou, GJ; Qu, B; Zhou, HB; Qin, YT; He, YK; Ma, JY; Yin, ZH; Ye, ZZ; Qian, J; Jiang, Q; Wu, LH; Guo, Q; Chen, S; Huang, CX; Kottyan, LC; Weirauch, MT; Vinuesa, CG; Shen, N |
| 期刊/會(huì)議名稱 | SCIENCE |
| 論文年度 | 2024 |
| 論文類別 | |
| 摘要 | Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)-driven lupus, ZEB2 is essential for ABC formation and autoimmune pathology. ZEB2 binds to +20-kb myocyte enhancer factor 2b (Mef2b)'s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. ZEB2 also targets genes important for ABC specification and function, including Itgax. ZEB2-driven ABC differentiation requires JAK-STAT (Janus kinase-signal transducer and activator of transcription), and treatment with JAK1/3 inhibitor reduces ABC accumulation in autoimmune mice and patients. Thus, ZEB2 emerges as a driver of B cell autoimmunity. |
| 期 | 6681 |
| 卷 | 383 |
| 影響因子 | 44.7 |
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