Intestinal Tolerance Requires Gut Homing and Expansion of FoxP3+ Regulatory T Cells in the Lamina Propria

Usriansyah Hadis et al . Immunity. 34 , 237–246 (2011)

Speaker: Chia-Lun Tsai(蔡佳倫)                                   Time: 15:10-16:00, Sep 28, 2011

Commentator: Dr. Chi-Chang Shieh (謝奇璋醫師)     Place: Room 601

Abstract

Activation-induced regulated immune responses to intestinal antigens is referred to as oral tolerance, which is thought to originate in the gut-draining lymph nodes and  supported by the generation of FoxP3+ regulatory T (Treg) and local expansion Treg cells driven by intestinal macrophages in the lamina propria (LP). Previously results have showed depletion of FoxP3+ cells abolish established oral tolerance.In this study authors used the DEREG mice (expressed the diphtheria toxin receptor under control of the FoxP3+ promoter) to specifically investigated the role of FoxP3+ cells in oral tolerance, and used transgenic OT-II cells (recognized the model antigen OVA in the context of MHCII) isolated from OT-II Ly5.1+ donors and adoptively transferred to congenic Ly5.2+ wild-type recipients on day 5, and day 12. Results showed more than 50% of all Ly5.1+CD4+ OT-II T cells expressed FoxP3+ in the LP, and naive T cells differentiated into a FoxP3+ fate rather than expansion of low numbers of natural Treg cells, which accounted for major population of FoxP3+ Treg cells in the LP. Mice received BrdU with the drinking water started with the first OVA gavage and were analyzed at day 5 and 12. The increase percentage of antigen-specific FoxP3+ Treg cell in the LP might be due to selective proliferation. Oral tolerance was essential by gut homing that was assessed in wild-type, ITGB7-, and MADCAM1- deficient mice and the cells isolated from lymph nodes of OT-II mice were adoptively transferred to wild-type, ITGB7-, and MADCAM1-deficient mice. To reduce frequency of IL-10 production F4/80+CD11b+ MHCII cells and accumulation of FoxP3+ Treg cells in the LP, the authors found CX3CR1-deficient mice fail to mount oral tolerance in CX3CR1-deficient mice. In summary, the authors show in this study that oral tolerance induction comprising the generation of Treg cells in the gut-draining lymph nodes, followed by migration into the gut and subsequent expansion of Treg cells driven by intestinal macrophages.

References

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