GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response
GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response
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DOI：
10.1182/blood-2005-07-2760
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发表时间：
2006-03-01
期刊：
影响因子：
20.3
通讯作者：
Emilie, D
中科院分区：
文献类型：
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作者：
Cohen, N;Mouly, E;Emilie, D
白介素10和糖皮质激素抑制抗原提呈树突状细胞刺激T淋巴细胞的能力。我们发现GILZ(GC诱导的亮氨酸拉链)的诱导参与了这一现象。IL-10、地塞米松(DEX)和转化生长因子(TGF)β刺激单核细胞和CD34+细胞来源的未成熟DC产生GILZ。GILZ是地塞米松、IL-10和转化生长因子β对DC表达CD80、CD83、CD86、免疫球蛋白样转录物(ILT)-3和B7-H1表达以及DC功能改变的充要条件。GILZ刺激未成熟DC产生IL-10，并阻止CD40L激活的DC产生炎性趋化因子。相反，GILZ不能阻止CD40配体介导的吞噬抑制，这表明它影响DC成熟的某些方面，但不是所有方面。GILZ可阻止DC激活抗原特异性T淋巴细胞反应。患者服用GCs可刺激其循环抗原提呈细胞中GILZ的表达，从而导致接受GC治疗的患者的淋巴细胞反应较弱。因此，GILZ表达的调节是决定DC是否刺激T淋巴细胞的重要因素，而IL-10、GCs和转化生长因子β在影响DC功能和免疫反应与耐受之间的平衡方面具有共同的机制。
Interleukin (IL)-10 and glucocorticoids (GCs) inhibit the ability of antigen-presenting dendritic cells (DCs) to stimulate T lymphocytes. We show that induction of GILZ (GC-induced leucine zipper) is involved in this phenomenon. IL-10, dexamethasone (DEX), and transforming growth factor (TGF)beta stimulate GILZ production in human immature DCs derived from monocytes and from CD34(+) cells. GILZ is necessary and sufficient for DEX, IL-10, and TGF beta modulation of CD80, CD83, CD86, immunoglobulin-like transcript (ILT)-3, and B7-H1 expression by DCs, and alteration of DC functions. GILZ stimulates the production of IL-10 by immature DCs and prevents the production of inflammatory chemokines by CD40L-activated DCs. In contrast, GILZ does not prevent CD40 ligand-mediated inhibition of phagocytosis, indicating that it affects some but not all aspects of DC maturation. GILZ prevents DCs from activating antigen-specific T lymphocyte responses. Administration of GCs to patients stimulates GILZ expression in their circulating antigen-presenting cells, and this contributes to the weak lymphocyte responses of GC-treated patients. Thus, regulation of GILZ expression is an important factor determining the decision of DCs whether or not to stimulate T lymphocytes, and IL-10, GCs, and TGF beta share this mechanism for influencing DC functions and the balance between immune response and tolerance.