IL-6-C/EBPbeta signaling drives monocytic differentiation of murine cultured lymphoid progenitors with immunoregulatory properties

While lymphoid progenitors have demonstrated unexpected plasticity in vivo, their differentiation into myeloid cells under in vitro conditions has been largely dismissed as an artifact or biologically irrelevant. Consequently, the functional properties of these cells remain poorly characterized. In this study, we show that cultured common lymphoid progenitors (cCLPs) differentiate into CD11b+CD115+ monocytic cells (cCLP-Ms) via IL-6-C/EBPbeta signaling. Molecular and phenotypic analyses revealed that cCLP-Ms acquire essential features of myeloid cells, including innate immune sensor expression and phagocytic capacity, while retaining unique characteristics distinct from bone marrow-derived macrophages (BMDMs), such as reduced MHC class II expression and TNF-alpha production. Functionally, cCLP-Ms exhibit immunoregulatory properties, effectively suppressing IgE-mediated cutaneous allergic inflammation upon adoptive transfer. These findings highlight the plasticity of lymphoid progenitors and establish a robust platform for investigating the mechanisms underlying myeloid differentiation. This system not only deepens our understanding of hematopoietic cell lineage flexibility but also offers a foundation for exploring therapeutic applications in immune regulation and inflammation

尽管淋巴祖细胞在体内已展现出出人意料的可塑性，但它们在体外条件下向髓系细胞分化的现象，长期以来被广泛归因于实验人为假象，或被认为不具备生物学相关性。因此，此类细胞的功能特性至今仍未得到充分表征。本研究证实，体外培养的普通淋巴祖细胞（common lymphoid progenitors, cCLPs）可通过IL-6-C/EBPβ信号通路分化为CD11b+CD115+单核细胞（下称cCLP-Ms）。分子与表型分析显示，cCLP-Ms获得了髓系细胞的核心特征，包括天然免疫感受器表达与吞噬功能，同时保留了与骨髓来源巨噬细胞（bone marrow-derived macrophages, BMDMs）显著不同的独特属性，例如较低的主要组织相容性复合体II类（MHC II类）表达水平与肿瘤坏死因子-α（TNF-α）分泌能力。功能层面，cCLP-Ms展现出免疫调节特性，在过继转移后可有效抑制IgE介导的皮肤过敏性炎症。上述研究结果凸显了淋巴祖细胞的可塑性，为探究髓系分化的潜在机制搭建了可靠的研究平台。该体系不仅加深了我们对造血细胞谱系灵活性的认知，也为探索免疫调节与炎症相关的治疗应用提供了研究基础。