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体外获得树突状细胞(dendritic cells,DC)或其前体对基于DC的免疫治疗至关重要。之前有报道注射MIP-1α可使一群F4/80-B220-CD11c+DC前体通过表达CCR1和CCR5招募至外周血。本研究中给小鼠注射MIP-1α之后鉴定了一种新的亚群细胞,即CCR6+CCR1-CCR5-B220-CD11c+细胞。当加入GM-CSF、IL-4和TNF-α培养时,这群细胞可分化为具有典型形态学特征、表型及抗原提呈能力的成熟DC,称为CCR+DC前体。虽然MIP-1α并不驱动CCR+DC前体招募,但其可通过诱导外周血MIP-3α表达的上调来驱动B220-CD11c+DC前体中CCR+DC前体亚群的招募。此外,外源性地给予MIP-3α可显著增强MIP-1α诱导的DC前体招募,联合应用MIP-1α和MIP-3α招募的DC前体数量显著高于单独使用MIP-1α或MIP-3α。本研究进一步证明了MIP-1α诱导DC前体招募的机制,即除了通过CCR1和CCR5表达驱动DC招募之外,MIP-1α可通过诱导MIP-3α,间接驱动CCR+DC前体招募,扩大了B220-CD11c+DC前体细胞数量。因此,联合使用MIP-1α和MIP-3α可能成为大量收集适合于免疫治疗用DC的有效方法。
In vitro dendritic cells (DCs) or their precursors are crucial for DC-based immunotherapy. It has previously been reported that injection of MIP-1α recruits a population of F4 / 80-B220-CD11c + DC precursors to peripheral blood by expressing CCR1 and CCR5. In this study, mice were injected with MIP-1α to identify a new subset of cells, CCR6 + CCR1-CCR5-B220-CD11c + cells. When cultured with GM-CSF, IL-4 and TNF-α, these cells differentiate into mature DCs with typical morphological features, phenotypes and antigen-presenting capabilities, called CCR + DC precursors. Although MIP-1α does not drive recruitment of CCR + DC precursors, it can drive the recruitment of CCR + DC precursor subpopulations in B220-CD11c + DC precursors by inducing the up-regulation of MIP-3α expression in peripheral blood. In addition, exogenous administration of MIP-3α significantly increased MIP-1α-induced DC precursor recruitment compared with MIP-1α or MIP-3α alone . This study further demonstrates the mechanism by which MIP-1α induces the recruitment of DC precursors. In addition to DC recruitment via CCR1 and CCR5 expression, MIP-1α indirectly recruits CCR + DC precursors by induction of MIP-3α, expanding B220-CD11c + DC precursor cells. Therefore, the combined use of MIP-1α and MIP-3α may be an effective method for collecting a large number of DCs suitable for immunotherapy.