Type II-activated murine macrophages produce IL-4.

Type II-activated murine macrophages produce IL-4.
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DOI:
10.1371/journal.pone.0046989
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kyle R
Kyle R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
La Flamme AC;Kharkrang M;Stone S;Mirmoeini S;Chuluundorj D;Kyle R

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已知巨噬细胞的II型活化支持Th 2应答的发展;然而,Th 2细胞因子(特别是IL-4)对II型活化的作用尚不清楚。为了评估中枢Th 2细胞因子IL-4是否可以改变巨噬细胞的II型活化,我们比较了野生型(WT)和IL-4 R α缺陷小鼠骨髓源性巨噬细胞在体外经典活化或II型活化的能力。我们发现,尽管WT和IL-4 R α缺陷型巨噬细胞都可以被LPS经典激活或被免疫复合物加LPS激活II型,但IL-4 R α缺陷型巨噬细胞始终产生比WT巨噬细胞高得多的IL-12 p40和IL-10水平。此外,我们发现来自两种菌株的II型巨噬细胞都能够产生IL-4;然而,这种IL-4不是WT小鼠产生的IL-12 p40和IL-10水平降低的原因。相反,我们发现衍生培养条件(GM-CSF + IL-3 vs M-CSF)可以解释BALB/c和IL-4 R α−/−巨噬细胞的不同反应,这些细胞因子塑造了随后的巨噬细胞,使得GM-CSF + IL-3促进更多的IL-12和IL-4,而M-CSF导致更高的IL-10产生。最后,我们发现IL-4产生的增强是II型活化状态的特征,因为其他II型活化产物显示出类似的结果。总之,这些结果暗示II型活化的巨噬细胞作为IL-4的重要先天免疫来源,其在形成适应性免疫应答中可能起重要作用。
Type II activation of macrophages is known to support Th2 responses development; however, the role of Th2 cytokines (esp. IL-4) on type II activation is unknown. To assess whether the central Th2 cytokine IL-4 can alter type II activation of macrophages, we compared the ability of bone marrow-derived macrophages from wild type (WT) and IL-4Rα-deficient mice to be classically or type II-activated in vitro. We found that although both WT and IL-4Rα-deficient macrophages could be classically activated by LPS or type II activated by immune complexes plus LPS, IL-4Rα-deficient macrophages consistently produced much higher levels of IL-12p40 and IL-10 than WT macrophages. Additionally, we discovered that type II macrophages from both strains were capable of producing IL-4; however, this IL-4 was not responsible for the reduced IL-12p40 and IL-10 levels produced by WT mice. Instead, we found that derivation culture conditions (GM-CSF plus IL-3 versus M-CSF) could explain the different responses of BALB/c and IL-4Rα−/− macrophages, and these cytokines shaped the ensuing macrophage such that GM-CSF plus IL-3 promoted more IL-12 and IL-4 while M-CSF led to higher IL-10 production. Finally, we found that enhanced IL-4 production is characteristic of the type II activation state as other type II-activating products showed similar results. Taken together, these results implicate type II activated macrophages as an important innate immune source of IL-4 that may play an important role in shaping adaptive immune responses.
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