TGFβR 信号传导控制肠道中 CD103+CD11b+ 树突状细胞的发育。,Nature Communications

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TGFβR 信号传导控制肠道中 CD103+CD11b+ 树突状细胞的发育。
Nature Communications ( IF 14.7 ) Pub Date : 2017-09-20 , DOI: 10.1038/s41467-017-00658-6
C C Bain _{1,

2} , J Montgomery ₁ , C L Scott _{1,

3,

4} , J M Kel ₅ , M J H Girard-Madoux ₅ , L Martens _{4,

6} , T F P Zangerle-Murray _{1,

7} , J Ober-Blöbaum _{5,

8} , D Lindenbergh-Kortleve ₉ , J N Samsom ₉ , S Henri ₁₀ , T Lawrence ₁₀ , Y Saeys _{6,

11} , B Malissen ₁₀ , M Dalod ₁₀ , B E Clausen _{5,

8} , A McI Mowat ₁

Affiliation

Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, G12 8TJ, UK.
The University of Edinburgh/MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGent Center for Inflammation Research, Technologiepark, Ghent 927, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, 9000, Belgium.
Department of Immunology, Erasmus MC, University Medical Center, 3015 GE, Rotterdam, The Netherlands.
Data Mining and Modeling for Biomedicine, VIB Inflammation Research Center, Ghent, 9052, Belgium.
Faculty of Biology, Medicine and Health and Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, M13 9PT, UK.
Institute for Molecular Medicine, University Medical Centre of the Johannes Gutenberg University, 55131, Mainz, Germany.
Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands.
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288, Marseille, France.
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, 9000, Belgium.

CD103 ⁺ CD11b ⁺树突状细胞 (DC) 是肠道所特有的，但控制其分化的因素尚不清楚。在这里，我们证明转化生长因子受体 1 (TGFβR1) 在这些细胞的发育中具有不可或缺的细胞内在作用。Tgfbr1 的缺失导致肠道 CD103 ⁺ CD11b ^{+ DC 明显减少，而 CD103}^- CD11b ⁺树突状细胞亚群相应增加。转录谱鉴定了定义 CD103 ⁺ CD11b ⁺ DC 谱系的标记，包括 CD101、TREM1 和 Siglec-F，并显示CD11c-Cre.Tgfbr1 ^fl/fl小鼠中不存在 CD103 + ^CD11b + ^DC ，反映了与 CD103 的分化缺陷^- CD11b ⁺中间体，而不是 CD103 表达的孤立丧失。^{CD103 +} CD11b ⁺ DC的缺陷伴随着体外和体内抗原特异性、可诱导性 FoxP3 ⁺调节性 T 细胞生成的减少，以及肠粘膜内源性 Th17 细胞数量的减少。因此，TGFβR1 介导的信号传导可以解释这些独特 DC 的组织特异性发育。肠道中不同树突状细胞 (DC) 亚群的发育线索尚未确定。作者在此表明，TGFβR1 信号传导是 CD103 ^- CD11b ^{+细胞发育成 CD103}⁺ CD11b ⁺肠 DC所必需的，并且它们有助于 Th17 和调节性 T 细胞的生成。

"点击查看英文标题和摘要"

TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine.

CD103⁺CD11b⁺ dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103⁺CD11b⁺ DCs and a reciprocal increase in the CD103^-CD11b⁺ dendritic cell subset. Transcriptional profiling identifies markers that define the CD103⁺CD11b⁺ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103⁺CD11b⁺ DCs in CD11c-Cre.Tgfbr1 ^fl/fl mice reflects defective differentiation from CD103^-CD11b⁺ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103⁺CD11b⁺ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3⁺ regulatory T cells in vitro and in vivo, and by reduced numbers of endogenous Th17 cells in the intestinal mucosa. Thus, TGFβR1-mediated signalling may explain the tissue-specific development of these unique DCs.Developmental cues for the different dendritic cell (DC) subsets in the intestine are yet to be defined. Here the authors show that TGFβR1 signalling is needed for development of CD103⁺CD11b⁺ intestinal DCs from CD103^-CD11b⁺ cells and that they contribute to the generation of Th17 and regulatory T cells.

更新日期：2017-09-20

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