Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPARγ
Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPARγ
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DOI：
10.1182/blood-2006-04-016840
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发表时间：
2007-01-15
期刊：
影响因子：
20.3
通讯作者：
Rajnavolgyi, Eva
中科院分区：
文献类型：
--
作者：
Gogolak, Peter;Rethi, Bence;Rajnavolgyi, Eva
越来越多的数据表明，树突状细胞的微环境调节亚型分化和CD 1表达，但外源性因素赋予这些作用的机制知之甚少。在这里，我们描述了依赖于CD 1a（-）单核细胞衍生的树突状细胞（moDC）的发展与过氧化物酶体增殖物激活受体γ（PPAR γ）的表达相关的脂质。我们还显示了未成熟的CD 1a（-）PPAR γ（+）moDCs向CD 1a（+）PPAR γ（-）细胞的连续分化受血清脂蛋白的限制并被促炎细胞因子终止。未成熟的CD 1a（-）moDCs具有比CD 1a（+）细胞更高的内化能力，而两种活化亚型具有相似的迁移潜力，但其细胞因子和趋化因子谱不同，这转化为不同的T淋巴细胞极化能力。CD 1a + moDC因其分泌大量IL-12 p70和CCL 1的能力而突出。由于脂蛋白使moDC分化倾向于产生CD 1a（-）PPAR γ（+）细胞，并抑制CD 1a（+）PPAR γ（-）细胞的发育，我们认为脂质的摄取导致内源性PPAR γ激动剂诱导基因转录级联反应，协调脂质代谢、脂质呈递CD 1分子的表达、亚型二分法和功能。淋巴结和肺朗格汉斯细胞组织细胞增生症中存在CD 1a（-）PPAR γ（+）和CD 1a（+）PPAR γ（-）DC，证实了这些DC亚群在体内的功能相关性。
Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation and CD1 expression, but the mechanisms by which exogenous factors confer these effects are poorly understood. Here we describe the dependence of CD1a(-) monocyte-derived dendritic cell (moDC) development on lipids associated with the expression of peroxisome proliferator-activated receptor-gamma (PPAR gamma). We also show the consecutive differentiation of immature CD1a(-)PPAR gamma(+) moDCs to CDla(+)PPAR gamma(-) cells limited by serum lipoproteins and terminated by proinflammatory cytokines. Immature CD1a(-)moDCs possess higher internalizing capacity than CD1a(+) cells, whereas both activated subtypes have similar migratory potential but differ in their cytokine and chemokine profiles, which translates to distinct T-lymphocyte-polarizing capacities. CD1a+ moDCs stand out by their capability to secrete high amounts of IL-12p70 and CCL1. As lipoproteins skew moDC differentiation toward the generation of CD1a(-)PPAR gamma(+) cells and inhibit the development of CD1a(+)PPAR gamma(-) cells, we suggest that the uptake of lipids results in endogenous PPAR gamma agonists that induce a cascade of gene transcription coordinating lipid metabolism, the expression of lipid-presenting CD1 molecules, subtype dichotomy, and function. The presence of CD1a(-)PPAR gamma(+) and CD1a(+)PPAR gamma(-) DCs in lymph nodes and in pulmonary Langerhans cell histiocytosis confirms the functional relevance of these DC subsets in vivo.