Origin of the lamina propria dendritic cell network.

Origin of the lamina propria dendritic cell network.
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DOI:
10.1016/j.immuni.2009.08.010
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发表时间:
2009-09-18
期刊:
影响因子:
32.4
通讯作者:
Merad M
Merad M
中科院分区:
医学1区
文献类型:
--
作者:
Bogunovic M;Ginhoux F;Helft J;Shang L;Hashimoto D;Greter M;Liu K;Jakubzick C;Ingersoll MA;Leboeuf M;Stanley ER;Nussenzweig M;Lira SA;Randolph GJ;Merad M

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肠道固有层(LP)中的CX 3CR 1+和CD 103+树突状细胞(DC)在黏膜免疫中起着关键作用。然而,起源和发展的途径,调节其分化的LP仍不清楚。我们的研究结果表明,单核细胞在M-CSFR和Flt 3配体的控制下专门产生CX 3CR 1 + CD 103 − LP DC。相比之下,共同DC祖细胞(CDP)和pre-DC,产生淋巴器官DC而不是单核细胞,在Flt 3配体和GM-CSF的控制下,仅分化为CD 103 + CX 3CR 1 − LP DC。LP中的CD 103 + CX 3CR 1 − DC而非CX 3CR 1 + CD 103 − DC组成型表达CCR 7,并且是第一个将致病性沙门氏菌从肠道转运到肠系膜淋巴结的DC。总而言之,这些结果强调了LP DC网络的多样性起源,并鉴定了由前DC产生的粘膜DC作为肠道免疫系统的关键哨兵。
CX3CR1+ and CD103+ dendritic cells (DCs) in intestinal lamina propria (LP) play a key role in mucosal immunity. However, the origin and the developmental pathways that regulate their differentiation in the LP remain unclear. Our results reveal that monocytes give rise exclusively to CX3CR1+CD103− LP DCs under the control of M-CSFR and Flt3 ligands. In contrast, common DC progenitors (CDP) and pre-DCs, which give rise to lymphoid organ DCs but not to monocytes, differentiate exclusively into CD103+CX3CR1− LP DCs under the control of Flt3 ligand and GM-CSF. CD103+CX3CR1− DCs but not CX3CR1+CD103− DCs in the LP constitutively express CCR7 and are the first DCs to transport pathogenic Salmonella from the intestinal tract to the mesenteric lymph nodes. Altogether, these results underline the diverse origin of the LP DC network and identify mucosal DCs that arise from pre-DC as key sentinels of the gut immune system.
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