Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg
Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg
复制标题
DOI：
10.1002/eji.200939782
复制
发表时间：
2010-04-01
影响因子：
5.4
通讯作者：
Hu, Jim
中科院分区：
文献类型：
--
作者：
Kushwah, Rahul;Wu, Jing;Hu, Jim
在癌症和脓毒症患者中已经观察到DC的凋亡，DC凋亡的缺陷与自身免疫性疾病的发生有关。然而，树突状细胞凋亡如何影响免疫反应的机制尚不清楚。在这项研究中，我们证明了未成熟的活性DC具有摄取凋亡性和坏死性DC的能力，而不被未成熟的活性DC识别为炎症事件。然而，凋亡DC的特异性摄取将未成熟的活性DC转化为耐受性DC，这些DC对内毒素诱导的成熟具有抵抗力。这些耐受树突状细胞分泌高水平的转化生长因子-β1，从而诱导初始T细胞分化为Foxp3(+)Treg。此外，只有在活体DC摄取了凋亡的DC而不是凋亡的脾细胞时，才能诱导Treg分化，这表明正是凋亡DC的特异性摄取使存活的未成熟DC具有诱导Foxp3(+)Treg的潜力。综上所述，这些发现确定存活的未成熟DC摄取凋亡性DC是一种免疫耐受事件。
DC apoptosis has been observed in patients with cancer and sepsis, and defects in DC apoptosis have been implicated in the development of autoimmune diseases. However, the mechanisms of how DC apoptosis affects immune responses, are unclear. In this study, we showed that immature viable DC have the ability to uptake apoptotic DC as well as necrotic DC without it being recognized as an inflammatory event by immature viable DC. However, the specific uptake of apoptotic DC converted immature viable DC into tolerogenic DC, which were resistant to LPS-induced maturation. These tolerogenic DC secreted increased levels of TGF-beta 1, which induced differentiation of naive T cells into Foxp3(+) Treg. Furthermore, induction of Treg differentiation only occurred upon uptake of apoptotic DC and not apoptotic splenocytes by viable DC, indicating that it is specifically the uptake of apoptotic DC that gives viable immature DC the potential to induce Foxp3(+) Treg. Taken together, these findings identify uptake of apoptotic DC by viable immature DC as an immunologically tolerogenic event.