Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function
Mast cells promote Th1 and Th17 responses by modulating dendritic cell maturation and function
复制标题
DOI：
10.1002/eji.201040994
复制
发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Maurer, Marcus
中科院分区：
文献类型：
--
作者：
Dudeck, Anne;Suender, Cathleen A.;Maurer, Marcus
肥大细胞在调节机体对病原体的保护性适应性免疫反应中起着重要作用。然而，目前尚不清楚MC是否通过直接作用于T细胞或通过修饰抗原呈递细胞的功能来促进这种宿主防御反应。为了确定MCs免疫调节能力的潜在机制，我们研究了MCs对树突状细胞（DC）成熟和功能的影响。我们发现，小鼠腹膜MCs与未成熟DC发生直接串扰，诱导DC成熟，共刺激分子表达增强证明了这一点。此外，MC/DC相互作用导致T细胞调节细胞因子IFN-γ、IL-2、IL-6和TGF-β释放到共培养上清液中，并增加LPS成熟DC的IL-12 p70、IFN-γ、IL-6和TGF-β分泌。这种MC-“致敏的”DC随后诱导有效的CD 4（+）T细胞增殖。令人惊讶的是，我们观察到MC致敏的DC刺激CD 4（+）T细胞释放高水平的IFN-γ和IL-17，表明MC促进Th 1和Th 17应答。重申我们的体外研究结果，我们发现，MC缺陷小鼠在利什曼原虫感染的疾病进展增强与Th 1和Th 17细胞诱导受损。
Mast cells (MCs) play an important role in the regulation of protective adaptive immune responses against pathogens. However, it is still unclear whether MCs promote such host defense responses via direct effects on T cells or rather by modifying the functions of antigen-presenting cells. To identify the underlying mechanisms of the immunoregulatory capacity of MCs, we investigated the impact of MCs on dendritic cell (DC) maturation and function. We found that murine peritoneal MCs underwent direct crosstalk with immature DCs that induced DC maturation as evidenced by enhanced expression of costimulatory molecules. Furthermore, the MC/DC interaction resulted in the release of the T-cell modulating cytokines IFN-gamma, IL-2, IL-6 and TGF-beta into coculture supernatants and increased the IL-12p70, IFN-gamma, IL-6 and TGF-beta secretion of LPS-matured DCs. Such MC-"primed" DCs subsequently induced efficient CD4(+) T-cell proliferation. Surprisingly, we observed that MC-primed DCs stimulated CD4(+) T cells to release high levels of IFN-gamma and IL-17, demonstrating that MCs promote Th1 and Th17 responses. Confirming our in vitro findings, we found that the enhanced disease progression of MC-deficient mice in Leishmania major infection is correlated with impaired induction of both Th1 and Th17 cells.