免疫学
生物
免疫系统
树突状细胞
细胞生物学
肠粘膜
细胞分化
医学
遗传学
基因
内科学
作者
Iliyan D. Iliev,Ilaria Spadoni,Erika Mileti,Gianluca Matteoli,Angelica Sonzogni,Gianluca M. Sampietro,Diego Foschi,Flavio Caprioli,Giuseppe Viale,María Rescigno
出处
期刊:Gut
[BMJ]
日期:2009-06-30
卷期号:58 (11): 1481-1489
被引量:363
标识
DOI:10.1136/gut.2008.175166
摘要
Objective:
In mice, a subpopulation of gut dendritic cells (DCs) expressing CD103 drives the development of regulatory T (Treg) cells. Further, it was recently described that the cross-talk between human intestinal epithelial cells (IECs) and DCs helps in maintaining gut immune homeostasis via the induction of non-inflammatory DCs. In this study, an analysis was carried out to determine whether IECs could promote the differentiation of CD103+ tolerogenic DCs, and the function of primary CD103+ DCs isolated from human mesenteric lymph nodes (MLNs) was evaluated. Methods:
Monocyte-derived DCs (MoDCs) and circulating CD1c+ DCs were conditioned or not with supernatants from Caco-2 cells or IECs isolated from healthy donors or donors with Crohn’s disease and analysed for their ability to induce Treg cell differentiation. In some cases, transforming growth factor β (TGFβ), retinoic acid (RA) or thymic stromal lymphopoietin (TSLP) were neutralised before conditioning. CD103+ and CD103− DCs were sorted by fluorescence-activated cell sorting (FACS) from MLNs and used in Treg cell differentiation experiments. Results:
It was found that human IECs promoted the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3+ Treg cells. This control was lost in patients with Crohn’s disease and paralleled a reduced expression of tolerogenic factors by primary IECs. MoDCs differentiated with RA or IEC supernatant upregulated the expression of CD103. Consistently, human primary CD103+ DCs isolated from MLNs were endowed with the ability to drive Treg cell differentiation. This subset of DCs expressed CCR7 and probably represents a lamina propria-derived migratory population. Conclusions:
A population of tolerogenic CD103+ DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive Treg cell development.
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