Selective probiotic bacteria induce IL-10–producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin

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• 作者：Hermelijn H. Smits ; Anneke Engering ; Desiree van der Kleij ; Esther C. de Jong ; Kim Schipper ; Toni M.M. van Capel ; Bas A.J. Zaat ; Maria Yazdanbakhsh ; Eddy A. Wierenga ; Yvette van Kooyk ; Martien L. Kap
• 关键词：Human ; dendritic cells ; toll-like receptor ; dendritic cell– ; specific intercellular adhesion molecule 3– ; grabbing nonintegrin ; bacteria ; IL-10
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2005
• 出版时间：June 2005
• 年：2005
• 卷：115
• 期：6
• 页码：1260-1267
• 全文大小：305 K

文摘

Background

Lactobacilli are probiotic bacteria that are frequently tested in the management of allergic diseases or gastroenteritis. It is hypothesized that these probiotics have immunoregulatory properties and promote mucosal tolerance, which is in part mediated by regulatory T cells (Treg cells). On the basis of pathogenic or tissue-specific priming, dendritic cells (DC) acquire different T cell–instructive signals and drive the differentiation of naive T_H cells into either T_H1, T_H2, or regulatory effector T cells.

Objective

We studied in what way different species of lactobacilli prime human DCs for their ability to drive Treg cells.

Methods

Human monocyte-derived DCs were cultured in vitro with lactobacilli of different species.

Results

Two different species of lactobacilli, Lactobacillus reuteri and Lactobacillus casei, but not Lactobacillus plantarum, prime monocyte-derived DCs to drive the development of Treg cells. These Treg cells produced increased levels of IL-10 and were capable of inhibiting the proliferation of bystander T cells in an IL-10–dependent fashion. Strikingly, both L reuteri and L casei, but not L plantarum, bind the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Blocking antibodies to DC-SIGN inhibited the induction of the Treg cells by these probiotic bacteria, stressing that ligation of DC-SIGN can actively prime DCs to induce Treg cells.

Conclusions

The targeting of DC-SIGN by certain probiotic bacteria might explain their beneficial effect in the treatment of a number of inflammatory diseases, including atopic dermatitis and Crohn's disease.