Bollyky Paul L, Lord James D, Masewicz Susan A, Evanko Stephen P, Buckner Jane H, Wight Thomas N, Nepom Gerald T
Benaroya Research Institute, Seattle, WA 98101, USA.
J Immunol. 2007 Jul 15;179(2):744-7. doi: 10.4049/jimmunol.179.2.744.
Hyaluronan is a glycosaminoglycan present in the extracellular matrix. When hyaluronan is degraded during infection and injury, low m.w. forms are generated whose interactions influence inflammation and angiogenesis. Intact high m.w. hyaluronan, conversely, conveys anti-inflammatory signals. We demonstrate that high m.w. hyaluronan enhances human CD4(+)CD25(+) regulatory T cell functional suppression of responder cell proliferation, whereas low m.w. hyaluronan does not. High m.w. hyaluronan also up-regulates the transcription factor FOXP3 on CD4(+)CD25(+) regulatory T cells. These effects are only seen with activated CD4(+)CD25(+) regulatory T cells and are associated with the expression of CD44 isomers that more highly bind high m.w. hyaluronan. At higher concentrations, high m.w. hyaluronan also has direct suppressive effects on T cells. We propose that the state of HA in the matrix environment provides contextual cues to CD4(+)CD25(+) regulatory T cells and T cells, thereby providing a link between the innate inflammatory network and the regulation of adaptive immune responses.
透明质酸是一种存在于细胞外基质中的糖胺聚糖。在感染和损伤过程中，当透明质酸被降解时，会产生低分子量形式，其相互作用会影响炎症和血管生成。相反，完整的高分子量透明质酸会传递抗炎信号。我们证明，高分子量透明质酸增强了人CD4(+)CD25(+)调节性T细胞对反应细胞增殖的功能抑制，而低分子量透明质酸则没有。高分子量透明质酸还上调CD4(+)CD25(+)调节性T细胞上的转录因子FOXP3。这些效应仅在活化的CD4(+)CD25(+)调节性T细胞中可见，并且与更高亲和力结合高分子量透明质酸的CD44异构体的表达有关。在更高浓度下，高分子量透明质酸对T细胞也有直接抑制作用。我们提出，基质环境中透明质酸的状态为CD4(+)CD25(+)调节性T细胞和T细胞提供背景线索，从而在先天性炎症网络和适应性免疫反应调节之间建立联系。
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