Background

Exposure to dietary constituents through the mucosal surface of the gastrointestinal tract generates oral tolerance that prevents deleterious T cell–mediated immunity. Although oral tolerance is an active process that involves emergence of CD4⁺ forkhead box p3 (Foxp3)⁺ regulatory T (Treg) cells in gut-associated lymphoid tissues (GALTs) for suppression of effector T (Teff) cells, how antigen-presenting cells initiate this process remains unclear.

Objective

We sought to determine the role of plasmacytoid dendritic cells (pDCs), which are known as unconventional antigen-presenting cells, in establishment of oral tolerance.

Methods

GALT-associated pDCs in wild-type mice were examined for their ability to induce differentiation of CD4⁺ Teff cells and CD4⁺Foxp3⁺ Treg cells in vitro. Wild-type and pDC-ablated mice were fed oral antigen to compare their intestinal generation of CD4⁺Foxp3⁺ Treg cells and induction of oral tolerance to protect against Teff cell–mediated allergic inflammation.

Results

GALT-associated pDCs preferentially generate CD4⁺Foxp3⁺ Treg cells rather than CD4⁺ Teff cells, and such generation requires an autocrine loop of TGF-β for its robust production. A deficiency of pDCs abrogates antigen-specific de novo generation of CD4⁺Foxp3⁺ Treg cells occurring in GALT after antigenic feeding. Furthermore, the absence of pDCs impairs development of oral tolerance, which ameliorates the progression of delayed-type hypersensitivity and systemic anaphylaxis, as well as allergic asthma, accompanied by an enhanced antigen-specific CD4⁺ Teff cell response and antibody production.

Conclusion

pDCs are required for establishing oral tolerance to prevent undesirable allergic responses, and they might serve a key role in maintaining gastrointestinal immune homeostasis.

中文翻译：

---

浆细胞样树突状细胞在诱导口腔耐受中的关键作用

背景

通过胃肠道粘膜表面接触饮食成分会产生口服耐受性，从而阻止有害的T细胞介导的免疫力。尽管口服耐受是一个活跃的过程，涉及在肠道相关淋巴组织（GALTs）中出现CD4 ⁺叉头盒p3（Foxp3）⁺调节性T（Treg）细胞的出现，以抑制效应性T（Teff）细胞，但抗原呈递细胞如何启动此过程尚不清楚。

客观的

我们试图确定浆液样树突状细胞（pDCs）在建立口服耐受性中的作用，称为非常规抗原呈递细胞。

方法

检测了野生型小鼠中与GALT相关的pDC的体外诱导CD4 ⁺ Teff细胞和CD4 ⁺ Foxp3 ⁺ Treg细胞分化的能力。给野生型和pDC消融的小鼠喂食口服抗原，以比较它们的肠道CD4 ⁺ Foxp3 ⁺ Treg细胞生成以及诱导口服耐受以保护Teff细胞介导的变应性炎症。

结果

与GALT相关的pDC优先生成CD4 ⁺ Foxp3 ⁺ Treg细胞，而不是CD4 ⁺ Teff细胞，并且这种生成需要TGF-β的自分泌环才能稳定产生。pDC的缺乏消除了抗原喂养后在GALT中发生的CD4 ⁺ Foxp3 ⁺ Treg细胞的抗原特异性从头产生。此外，pDC的缺乏会削弱口服耐受性的发展，从而改善迟发型超敏反应和全身过敏反应以及过敏性哮喘的进展，并伴随着抗原特异性CD4 ⁺ Teff细胞应答和抗体产生的增强。

结论

pDC是建立口服耐受性以防止不良的过敏反应所必需的，它们可能在维持胃肠道免疫稳态方面起关键作用。