Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2011;6(8):e23618. doi: 10.1371/journal.pone.0023618. Epub 2011 Aug 23.
Type 1 regulatory T (Tr1) cells, characterized by the secretion of high levels of the anti-inflammatory cytokine interleukin-10 (IL-10), play an important role in the regulation of autoimmune diseases and transplantation. However, effective strategies that specifically induce Tr1 cells in vivo are limited. Furthermore, the pathways controlling the induction of these cells in vivo are not well understood.
METHODOLOGY/PRINCIPAL FINDINGS: Here we report that nasal administration of anti-CD3 antibody induces suppressive Tr1 cells in mice. The in vivo induction of Tr1 cells by nasal anti-CD3 is dependent on IL-27 produced by upper airway resident dendritic cells (DCs), and is controlled by the transcription factors aryl hydrocarbon receptor (AHR) and c-Maf. Subsequently, IL-21 acts in an autocrine fashion to expand and maintain the Tr1 cells induced in vivo by nasally administered anti-CD3.
CONCLUSIONS/SIGNIFICANCE: Our findings identify a unique approach to generate Tr1 cells in vivo and provide insights into the mechanisms by which these cells are induced.
1 型调节性 T（Tr1）细胞的特征是高水平分泌抗炎细胞因子白细胞介素-10（IL-10），在自身免疫性疾病和移植的调节中发挥重要作用。然而，体内特异性诱导 Tr1 细胞的有效策略有限。此外，体内控制这些细胞诱导的途径也知之甚少。
方法/主要发现：在这里，我们报告鼻内给予抗 CD3 抗体可诱导小鼠产生抑制性 Tr1 细胞。鼻内抗 CD3 诱导 Tr1 细胞的体内诱导依赖于上呼吸道驻留树突状细胞（DCs）产生的白细胞介素-27（IL-27），并受转录因子芳香烃受体（AHR）和 c-Maf 控制。随后，IL-21 以自分泌的方式扩增和维持经鼻内给予抗 CD3 诱导的体内 Tr1 细胞。
结论/意义：我们的发现确定了一种在体内产生 Tr1 细胞的独特方法，并深入了解了诱导这些细胞的机制。
