Fibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-β receptor (LTβR) engagement, whereas LTβR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.

中文翻译：

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YAP / TAZ直接承诺和成熟的淋巴结成纤维网状细胞。

纤维母细胞网状细胞（FRC）是淋巴器官的免疫学专门成纤维细胞，而FRC成熟对于淋巴结（LNs）的结构和功能特性至关重要。在这里，我们显示HAP信号的最终效应器YAP和TAZ（YAP / TAZ）调节FRC的参与和成熟。YAP / TAZ在FRCs中的选择性消耗会损害FRC的生长和分化并损害LN的结构组织，而YAP / TAZ的过度活化会增强FRCs的肌成纤维细胞特征并加重LN纤维化。从机理上讲，YAP / TAZ和p52之间的相互作用促进了趋化因子表达，这是在淋巴毒素β受体（LTβR）参与之前进行FRC谱系定位所需的趋化因子表达，而LTβR激活则抑制了FAP成熟的YAP / TAZ活性。