Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA.
Nat Med. 2010 Oct;16(10):1128-33. doi: 10.1038/nm.2201. Epub 2010 Sep 12.
We propose that a C-type lectin receptor, SIGNR-1 (also called Cd209b), helps to condition dendritic cells (DCs) in the gastrointestinal lamina propria (LPDCs) for the induction of oral tolerance in a model of food-induced anaphylaxis. Oral delivery of BSA bearing 51 molecules of mannoside (Man(51)-BSA) substantially reduced the BSA-induced anaphylactic response. Man(51)-BSA selectively targeted LPDCs that expressed SIGNR1 and induced the expression of interleukin-10 (IL-10), but not IL-6 or IL-12 p70. We found the same effects in IL-10-GFP knock-in (tiger) mice treated with Man(51)-BSA. The Man(51)-BSA-SIGNR1 axis in LPDCs, both in vitro and in vivo, promoted the generation of CD4(+) type 1 regulatory T (Tr1)-like cells that expressed IL-10 and interferon-γ (IFN-γ), in a SIGNR-1- and IL-10-dependent manner, but not of CD4(+)CD25(+)Foxp3(+) regulatory T cells. The Tr1-like cells could transfer tolerance. These results suggest that sugar-modified antigens might be used to induce oral tolerance by targeting SIGNR1 and LPDCs.
我们提出 C 型凝集素受体 SIGNR-1（也称为 Cd209b）有助于调节胃肠道固有层（LPDC）中的树突状细胞（DC），从而在食物诱导过敏反应的模型中诱导口服耐受。BSA 结合 51 个甘露糖分子（Man(51)-BSA）的口服给予大大降低了 BSA 诱导的过敏反应。Man(51)-BSA 选择性靶向表达 SIGNR1 的 LPDC，并诱导白细胞介素-10（IL-10）的表达，但不诱导 IL-6 或 IL-12 p70 的表达。我们在接受 Man(51)-BSA 治疗的 IL-10-GFP 敲入（老虎）小鼠中发现了相同的作用。Man(51)-BSA-SIGNR1 轴在 LPDC 中，无论是在体外还是体内，都以 SIGNR-1 和 IL-10 依赖的方式促进表达白细胞介素-10（IL-10）和干扰素-γ（IFN-γ）的 CD4+1 型调节性 T（Tr1）样细胞的产生，但不产生 CD4+CD25+Foxp3+调节性 T 细胞。Tr1 样细胞可以传递耐受。这些结果表明，糖修饰的抗原可能通过靶向 SIGNR1 和 LPDC 用于诱导口服耐受。
