Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization.

Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization.
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DOI:
10.1371/journal.pone.0025660
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Murphy KM
Murphy KM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Edelson BT;Bradstreet TR;KC W;Hildner K;Herzog JW;Sim J;Russell JH;Murphy TL;Unanue ER;Murphy KM

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树突状细胞(DCs)亚群在前体细胞起源、功能特性、生长因子需求和对转录因子的依赖性方面存在差异。淋巴组织常住CD8α+常规dc (cdc)和CD11blow/−CD103+非淋巴样dc是发育相关的,它们都依赖于fms样酪氨酸激酶3配体(Flt3L),并且需要转录因子Batf3、Irf8和Id2来发育。最近有研究表明,粒细胞/巨噬细胞集落刺激因子(GM-CSF)是真皮CD11blow/ - Langerin+CD103+ DC发展所必需的,并且这种真皮DC亚群是实验性自身免疫性脑炎(EAE)中启动自身反应性T细胞所必需的。在这里,我们比较了GM-CSF受体缺陷(Csf2rb−/−)和Batf3−/−小鼠外周组织dc的发展和对EAE的易感性。我们发现batf3依赖性真皮CD11blow/ - Langerin+ dc确实在Csf2rb - / -小鼠中发育,但它们表达的CD103水平降低,但并非缺失。此外,缺乏所有外周CD11blow/−dc的Batf3−/−小鼠在皮下免疫后表现出强大的Th细胞启动,并且对EAE敏感。我们的研究结果表明,Csf2rb - / -小鼠表现出的T效应启动缺陷和对EAE的抗性不是由于缺乏真皮CD11blow/ - Langerin+CD103+ dc。
Dendritic cells (DCs) subsets differ in precursor cell of origin, functional properties, requirements for growth factors, and dependence on transcription factors. Lymphoid-tissue resident CD8α+ conventional DCs (cDCs) and CD11blow/−CD103+ non-lymphoid DCs are developmentally related, each being dependent on FMS-like tyrosine kinase 3 ligand (Flt3L), and requiring the transcription factors Batf3, Irf8, and Id2 for development. It was recently suggested that granulocyte/macrophage colony stimulating factor (GM-CSF) was required for the development of dermal CD11blow/−Langerin+CD103+ DCs, and that this dermal DC subset was required for priming autoreactive T cells in experimental autoimmune encephalitis (EAE). Here, we compared development of peripheral tissue DCs and susceptibility to EAE in GM-CSF receptor deficient (Csf2rb −/−) and Batf3 −/− mice. We find that Batf3-dependent dermal CD11blow/−Langerin+ DCs do develop in Csf2rb −/− mice, but that they express reduced, but not absent, levels of CD103. Further, Batf3 −/− mice lacking all peripheral CD11blow/− DCs show robust Th cell priming after subcutaneous immunization and are susceptible to EAE. Our results suggest that defective T effector priming and resistance to EAE exhibited by Csf2rb −/− mice does not result from the absence of dermal CD11blow/−Langerin+CD103+ DCs.
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