Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A.

Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A.
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DOI:
10.1038/ni.1942
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发表时间:
2010-11
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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中性粒细胞是炎症过程中的主要效应细胞,但也可以通过分泌抗炎细胞因子来控制过度的炎症反应。然而,调节其可塑性的机制仍不清楚。我们现在表明,系统性血清淀粉样蛋白A-1(SAA-1)控制中性粒细胞分化的可塑性。SAA-1不仅诱导分泌抗炎IL-10的中性粒细胞,而且还促进了不变NKT(iNKT)细胞与这些中性粒细胞的相互作用,这是一个通过减少IL-10和增强IL-12产生来限制其抑制活性的过程。由于产生SAA-1的黑色素瘤促进分泌IL-10的中性粒细胞的分化,因此利用iNKT细胞可以通过降低免疫抑制性中性粒细胞的频率和恢复肿瘤特异性免疫应答来治疗。
Neutrophils are the primary effector cells during inflammation, but can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms modulating their plasticity remain unclear. We now show that systemic serum amyloid A-1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory IL-10-secreting neutrophils but also promoted invariant NKT (iNKT) cell interaction with these neutrophils, a process that limits their suppressive activity by reducing IL-10 and enhancing IL-12 production. Because SAA-1-producing melanomas promote differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by reducing the frequency of immunosuppressive neutrophils and restoring tumor specific immune responses.
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