Continuous retinoic acid induces the differentiation of mature regulatory monocytes but fails to induce regulatory dendritic cells.
Continuous retinoic acid induces the differentiation of mature regulatory monocytes but fails to induce regulatory dendritic cells.
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DOI：
10.1186/1471-2172-15-8
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发表时间：
2014-02-18
期刊：
影响因子：
3
通讯作者：
Papenfuss TL
中科院分区：
文献类型：
--
作者：
VanGundy ZC;Guerau-de-Arellano M;Baker JD;Strange HR;Olivo-Marston S;Muth DC;Papenfuss TL
髓样细胞(MC)具有强大的免疫调节能力，可用于治疗炎症性疾病。然而，促进调节髓系细胞分化的因素仍然知之甚少。我们之前已经证明，雌三醇(E3)在体内可以诱导成熟的调节性树突状细胞。为了确定附加的类固醇激素是否可以诱导成熟的调节性髓系细胞，我们研究了维甲酸(RA)对MC的影响。维甲酸是一种类固醇激素，在调节肠道粘膜免疫和促进髓系分化方面具有重要作用。我们假设在分化过程中RA的存在将促进成熟的调节性髓系细胞(MCregs)的形成。为了确定RA诱导调节性髓系细胞的能力，我们在RA的影响下用粒细胞-巨噬细胞集落刺激因子(GM-CSF)分化骨髓祖细胞。我们发现，在RA存在下分化的第7天的MC，成熟标志(CD80、CD86和MHCII)和抑制标志(PD-L1和PD-L2)的阳性百分率和相对表达水平均高于对照细胞。在功能上，这7天的RA MC在细胞内表达IL-10，在体外诱导调节性T细胞，并抑制应答免疫细胞的增殖，即使在炎性刺激后也是如此。RA诱导成熟的调节性髓系细胞，这些细胞是抑制性的，具有CD11b+CD11c-Ly6C低/中单核细胞表型。令人惊讶的是，RA CD11c+树突状细胞没有抑制作用，可以促进增殖。这些结果表明，在单核细胞和树突状细胞生成过程中，持续性RA对不同的髓系细胞群有独特的作用，并促进调节性单核细胞的形成。
Myeloid cells (MC) have potent immunoregulatory abilities that can be therapeutically useful to treat inflammatory disease. However, the factors which promote regulatory myeloid cell differentiation remain poorly understood. We have previously shown that estriol (E3) induces mature regulatory dendritic cells in vivo. To determine whether additional steroid hormones could induce mature regulatory myeloid cells, we investigated the effects of retinoic acid (RA) on MCs. Retinoic acid is a steroid hormone important in regulating mucosal immunity in the gut and promoting myeloid differentiation. We hypothesized that the presence of RA during differentiation would promote the formation of mature regulatory myeloid cells (MCregs). To determine RA’s ability to induce regulatory myeloid cells, we differentiated bone marrow progenitor cells with granulocytic-macrophage colony-stimulating factor (GM-CSF) under the influence of RA. We found that day 7 MCs differentiated in the presence of RA had an increase in the percent positive and relative expression levels of both maturation (CD80, CD86, and MHCII) and inhibitory (PD-L1 and PD-L2) markers compared to control cells. Functionally, these day 7 RA MCs expressed increased intracellular IL-10, induced regulatory T cells in vitro compared to controls and suppressed the proliferation of responder immune cells even after inflammatory challenge with LPS. RA induced mature regulatory myeloid cells that were suppressive and had a CD11b+ CD11c-Ly6C low/intermediate monocyte phenotype. Surprisingly, RA CD11c+ dendritic cells were not suppressive and could contribute to enhanced proliferation. These results suggest that continuous RA has unique effects on different myeloid populations during monopoeisis and dendropoiesis and promotes a population of regulatory monocytes.
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影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
1.5
作者：
Dong, XY;Bachman, LA;Griffin, MD
通讯作者：
Griffin, MD
影响因子：
15.9
作者：
ATHENS, JW;WINTROBE, MM;RAAB, SO
通讯作者：
RAAB, SO
DOI：
10.1186/2047-1440-1-11
发表时间：
2012-09-28
期刊：
Transplantation research
影响因子：
--
作者：
Geissler EK
通讯作者：
Geissler EK
影响因子：
3.2
作者：
Drumea, Karen;Yang, Zhong-fa;Rosmarin, Alan
通讯作者：
Rosmarin, Alan