MGL2+ Dermal Dendritic Cells Are Sufficient to Initiate Contact Hypersensitivity In Vivo
MGL2+ Dermal Dendritic Cells Are Sufficient to Initiate Contact Hypersensitivity In Vivo
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DOI：
10.1371/journal.pone.0005619
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发表时间：
2009-05-19
期刊：
影响因子：
3.7
通讯作者：
Irimura, Tatsuro
中科院分区：
文献类型：
--
作者：
Kumamoto, Yosuke;Denda-Nagai, Kaori;Irimura, Tatsuro
背景：树突状细胞（Dendritic cells，DCs）是哺乳动物免疫系统中最强的抗原提呈细胞。在皮肤中，表皮朗格汉斯细胞（LC）和真皮树突状细胞（DDC）调查侵入性病原体，并在迁移到皮肤淋巴结（LN）后将抗原呈递给T细胞。到目前为止，这两个DC亚群之间的功能和表型差异仍然不清楚，由于缺乏标志物，以确定DDCs.Methodology/主要调查结果：在本报告中，我们表明，巨噬细胞半乳糖型C型凝集素（MGL）2只表达在皮肤LN免疫系统的DDC子集。在皮肤中，MGL 2在真皮中的大多数（约88%）MHCII（+）CD 11 c（+）细胞上表达。在皮肤LN中，MGL 2表达仅限于B220（-）CD 8 alpha（lo）CD 11b（+）CD 11 c（+）MHCII（hi）组织来源的DC。在用FITC皮肤致敏后24 h内，MGL 2（+）DDC从真皮迁移到引流LN中。与LC不同，MGL 2（+）DDC位于外T细胞皮质中的高内皮微静脉附近。在FITC诱导的接触性超敏反应（CHS）中，将FITC（+）MGL 2（+）DDCs而非FITC（+）MGL 2（-）DCs过继转移到未处理小鼠中导致诱导FITC特异性耳肿胀，表明DDCs在皮肤免疫应答的启动中起关键作用。这些结果证明了MGL 2作为DDC的新标志物的可用性，并表明MGL 2（+）DDC对启动CHS的贡献。
Background: Dendritic cells (DCs) are the most potent antigen-presenting cells in the mammalian immune system. In the skin, epidermal Langerhans cells (LCs) and dermal dendritic cells (DDCs) survey for invasive pathogens and present antigens to T cells after migration to the cutaneous lymph nodes (LNs). So far, functional and phenotypic differences between these two DC subsets remain unclear due to lack of markers to identify DDCs.Methodology/Principal Findings: In the present report, we demonstrated that macrophage galactose-type C-type lectin (MGL) 2 was exclusively expressed in the DDC subset in the skin-to-LN immune system. In the skin, MGL2 was expressed on the majority (about 88%) of MHCII(+)CD11c(+) cells in the dermis. In the cutaneous LN, MGL2 expression was restricted to B220(-)CD8 alpha(lo)CD11b(+)CD11c(+)MHCII(hi) tissue-derived DC. MGL2(+)DDC migrated from the dermis into the draining LNs within 24 h after skin sensitization with FITC. Distinct from LCs, MGL2(+)DDCs localized near the high endothelial venules in the outer T cell cortex. In FITC-induced contact hypersensitivity (CHS), adoptive transfer of FITC(+)MGL2(+)DDCs, but not FITC(+)MGL2(-)DCs into naive mice resulted in the induction of FITC-specific ear swelling, indicating that DDCs played a key role in initiation of immune responses in the skin.Conclusions/Significance: These results demonstrated the availability of MGL2 as a novel marker for DDCs and suggested the contribution of MGL2(+) DDCs for initiating CHS.