Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells
Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells
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DOI：
10.1182/blood-2010-01-264150
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发表时间：
2010-12-23
期刊：
影响因子：
20.3
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
--
作者：
Tanizaki, Hideaki;Egawa, Gyohei;Kabashima, Kenji
树突状细胞（Dendritic cells，DC）是通过抗原获得、迁移、成熟和T细胞刺激来启动获得性免疫应答的关键细胞。这种反应的关键机制之一是肌动蛋白成核和聚合的过程，这是由几组蛋白质介导的，包括哺乳动物透明相关的formins（mDia）。然而，mDia在DC中的作用仍然未知。在此，我们研究了mDia 1（mDia的同种型之一）在DC中的作用。尽管对照C57 BL/6和mDia 1缺陷（mDia 1（-/-））小鼠之间骨髓来源的DC的增殖和成熟相当，但mDia 1（-/-）骨髓来源的DC对细胞基质的粘附和扩散受到损害。此外，在体内异硫氰酸荧光素诱导的皮肤DC向引流淋巴结的迁移以及体外向CCL 21的侵入性迁移和定向迁移在mDia 1（-/-）DC中受到抑制。此外，持续的T细胞相互作用和T细胞刺激淋巴结受损mDia 1缺陷。与此一致，DC依赖性迟发性超敏反应被mDia 1缺陷型DC减弱。这些结果表明，肌动蛋白聚合，这是介导的mDia 1，是必不可少的几个方面的DC启动获得性免疫反应。（血。2010;116（26）：5875-5884）
Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1(-/-)) mice, adhesion and spreading to cellular matrix were impaired in mDia1(-/-) bone marrow-derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1(-/-) DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses. (Blood. 2010;116(26):5875-5884)