GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity.
GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity.
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DOI：
10.1093/intimm/dxp003
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发表时间：
2009-04
影响因子：
4.4
通讯作者：
Iwata M
中科院分区：
文献类型：
--
作者：
Yokota A;Takeuchi H;Maeda N;Ohoka Y;Kato C;Song SY;Iwata M
由肠树突状细胞（DC）产生的视黄酸（RA）在淋巴细胞上印记肠道归巢特异性并增强Foxp 3+调节性T细胞分化。醛脱氢酶（ALDH）1A在这些DC中的表达对于RA的产生是必需的。然而，目前尚不清楚在无特定病原体（SPF）条件下如何诱导稳态ALDH 1A表达。在这里，我们发现，骨髓来源的树突状细胞（BM-DCs）与粒细胞-巨噬细胞集落刺激因子（GM-CSF）产生的表达Aldh 1a 2，Aldh 1a的亚型，但fms相关的酪氨酸激酶3配体产生的BM-DCs没有。来自正常SPF小鼠的肠系膜淋巴结（MLN）和派伊尔集合淋巴结（PP）的DC表达ALDH 1A 2，但不表达其他已知的RA产生酶。采用流式细胞术方法，我们在10-30%的PP-DCs和MLN-DCs中检测到ALDH活性。它们是CD 11高CD 4 −/低CD 8 α中CD 11 b −/低F4/80低/中CD 45 RB低CD 86高MHC II类高B220 − CD 103+。在体外脾DC中，GM-CSF和IL-4协同诱导同等水平的醛脱氢酶活性（ALDHact）和ALDH 1A 2表达。然而，在BM-DCs中，需要通过Toll样受体或RA受体的额外信号来诱导等效水平。产生的ALDH 1A 2 + DC触发T细胞表达肠道归巢受体或Foxp 3。GM-CSF受体缺陷或维生素A缺陷小鼠表现出肠DC中ALDHact和肠固有层中T细胞数量的显著减少，而IL-4受体介导的信号被抑制。GM-CSF+ CD 11 c −F4/80+细胞组成性存在于肠组织中。结果表明，在使肠道DC产生RA的多种微环境因素中，GM-CSF和RA本身是关键的。
Retinoic acid (RA) produced by intestinal dendritic cells (DCs) imprints gut-homing specificity on lymphocytes and enhances Foxp3+ regulatory T-cell differentiation. The expression of aldehyde dehydrogenase (ALDH) 1A in these DCs is essential for the RA production. However, it remains unclear how the steady-state ALDH1A expression is induced under specific pathogen-free (SPF) conditions. Here, we found that bone marrow-derived dendritic cells (BM-DCs) generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) expressed Aldh1a2, an isoform of Aldh1a, but that fms-related tyrosine kinase 3 ligand-generated BM-DCs did not. DCs from mesenteric lymph nodes (MLN) and Peyer's patches (PP) of normal SPF mice expressed ALDH1A2, but not the other known RA-producing enzymes. Employing a flow cytometric method, we detected ALDH activities in 10–30% of PP-DCs and MLN-DCs. They were CD11chighCD4−/lowCD8αintermediateCD11b−/low F4/80low/intermediateCD45RBlowCD86highMHC class IIhighB220−CD103+. Equivalent levels of aldehyde dehydrogenase activity (ALDHact) and ALDH1A2 expression were induced synergistically by GM-CSF and IL-4 in splenic DCs in vitro. In BM-DCs, however, additional signals via Toll-like receptors or RA receptors were required for inducing the equivalent levels. The generated ALDH1A2+ DCs triggered T cells to express gut-homing receptors or Foxp3. GM-CSF receptor-deficient or vitamin A-deficient mice exhibited marked reductions in the ALDHact in intestinal DCs and the T cell number in the intestinal lamina propria, whereas IL-4 receptor-mediated signals were dispensable. GM-CSF+CD11c−F4/80+ cells existed constitutively in the intestinal tissues. The results suggest that GM-CSF and RA itself are pivotal among multiple microenvironment factors that enable intestinal DCs to produce RA.
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DOI：
10.1084/jem.20080039
发表时间：
2008-10-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hammerschmidt SI;Ahrendt M;Bode U;Wahl B;Kremmer E;Förster R;Pabst O
通讯作者：
Pabst O
影响因子：
5.4
作者：
Dudda, JC;Lembo, A;Martin, SF
通讯作者：
Martin, SF
影响因子：
30.5
作者：
Denning, Timothy L.;Wang, Yi-Chong;Pulendran, Bali
通讯作者：
Pulendran, Bali
影响因子：
56.9
作者：
DRANOFF, G;CRAWFORD, AD;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
11.4
作者：
Huq, M. D. Mostaqul;Tsai, Nien-Pei;Wei, Li-Na
通讯作者：
Wei, Li-Na