Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells
Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells
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DOI：
10.4049/jimmunol.180.6.3680
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发表时间：
2008-03-15
影响因子：
4.4
通讯作者：
Torensma, Ruurd
中科院分区：
文献类型：
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作者：
den Dekker, Els;Grefte, Sander;Torensma, Ruurd
IL-4诱导单核细胞向树突状细胞（dc）分化。许多细胞因子的活性由糖胺聚糖（GAGs）调节。在本研究中，我们探讨了GAGs对il -4诱导单核细胞向DCs分化的影响。IL-4剂量依赖性上调dc特异性icam -3抓取非整合素（DC-SIGN）、CD80、CD206和CD1a的表达。单核细胞对硫酸肝素（HS）和硫酸软骨素（CS） B （CSB；硫酸皮肤素）的抗体染色阳性，但对CSA、CSC和CSE的抗体染色阴性。氯酸钠对单核细胞/DC细胞表面GAGs的磺化抑制降低了硫酸盐识别单链抗体的反应性。这与IL-4诱导的DC分化受阻有关，这可以通过降低DC- sign和CD1a的表达以及降低DC诱导的PBL增殖来证明，这表明磺化单核细胞表面GAGs支持IL-4活性。此外，通过软骨素酶ABC去除细胞表面的硫酸软骨素会强烈破坏il -4诱导的STAT6磷酸化，而通过肝素酶III去除HS则只有微弱的抑制作用。IL-4与肝素和CSB结合，但不与HS、CSA、CSC、CSD和CSE结合。IL-4的结合需要伊杜醛酸、n -硫酸盐基团（肝素）和特定的O -硫酸盐（CSB和肝素）。总之，这些数据表明单核细胞表面硫酸软骨素在il -4驱动的单核细胞向dc的分化中起重要作用。
IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), CD80, CD206, and CD1a. Monocytes stained positive with Abs against heparan sulfate (HS) and chondroitin sulfate (CS) B (CSB; dermatan sulfate), but not with Abs that recognize CSA, CSC, and CSE. Inhibition of sulfation of monocyte/DC cell surface GAGs by sodium chlorate reduced the reactivity of sulfate-recognizing single-chain Abs. This correlated with hampered IL-4-induced DC differentiation as evidenced by lower expression of DC-SIGN and CD1a and a decreased DC-induced PBL proliferation, suggesting that sulfated monocyte cell surface GAGs support IL-4 activity. Furthermore, removal of cell surface chondroitin sulfates by chondroitinase ABC strongly impaired IL-4-induced STAT6 phosphorylation, whereas removal of HS by heparinase III had only a weak inhibitory effect. IL-4 bound to heparin and CSB, but not to HS, CSA, CSC, CSD, and CSE. Binding of IL-4 required iduronic acid, an N-sulfate group (heparin) and specific O sulfates (CSB and heparin). Together, these data demonstrate that monocyte cell surface chondroitin sulfates play an important role in the IL-4-driven differentiation of monocytes into DCs.