Langhans multinucleated giant cells (LGCs) are a specific type of multinucleated giant cell containing a characteristic horseshoe-shaped ring of nuclei that are present within granulomas of infectious etiology. Although cytokines that trigger macrophage activation (such as IFN-γ) induce LGC formation, it is not clear whether cytokines that trigger macrophage differentiation contribute to LGC formation. Here, we found that IL-15, a cytokine that induces M1 macrophage differentiation, programs human peripheral blood adherent cells to form LGCs. Analysis of the IL-15‒treated adherent cell transcriptome identified gene networks for T cells, DNA damage and replication, and IFN-inducible genes that correlated with IL-15 treatment and LGC-type multinucleated giant cell formation. Gene networks enriched for myeloid cells were anticorrelated with IL-15 treatment and LGC formation. Functional studies revealed that T cells were required for IL-15‒induced LGC formation, involving a direct contact with myeloid cells through CD40L-CD40 interaction and IFN-γ release. These data indicate that IL-15 induces LGC formation through the direct interaction of activated T cells and myeloid cells.

Langhans 多核巨细胞 (LGC) 是一种特殊类型的多核巨细胞，含有特征性的马蹄形核环，存在于感染性肉芽肿中。尽管触发巨噬细胞活化的细胞因子（如 IFN-γ）诱导 LGC 形成，但尚不清楚触发巨噬细胞分化的细胞因子是否有助于 LGC 形成。在这里，我们发现 IL-15，一种诱导 M1 巨噬细胞分化的细胞因子，可以编程人外周血贴壁细胞以形成 LGC。对 IL-15 处理的贴壁细胞转录组的分析确定了T 细胞、DNA 损伤和复制以及IFN 诱导基因的基因网络这与 IL-15 处理和 LGC 型多核巨细胞形成相关。富含髓样细胞的基因网络与 IL-15 处理和 LGC 形成抗相关。功能研究表明，IL-15 诱导的 LGC 形成需要 T 细胞，包括通过 CD40L-CD40 相互作用和 IFN-γ 释放与骨髓细胞直接接触。这些数据表明 IL-15 通过活化的 T 细胞和骨髓细胞的直接相互作用诱导 LGC 形成。