Astrocytes as antigen-presenting cells: expression of IL-12/IL-23
Astrocytes as antigen-presenting cells: expression of IL-12/IL-23
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DOI：
10.1111/j.1471-4159.2005.03368.x
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发表时间：
2005-10-01
影响因子：
4.7
通讯作者：
Rostami, A
中科院分区：
文献类型：
--
作者：
Constantinescu, CS;Tani, M;Rostami, A
白细胞介素-12（IL-12，p70）是一种由p40和p35亚基组成的异源二聚体细胞因子，在Th 1型免疫应答中起重要作用，在多发性硬化（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）中起重要作用。最近，相关的异源二聚体细胞因子IL-23，由与IL-12相同的p40亚基和独特的p19亚基组成，被证明参与Th 1应答和EAE。我们研究了星形胶质细胞和小胶质细胞，具有抗原呈递细胞（APC）功能的CNS细胞是否可以将抗原呈递给髓鞘碱性蛋白（MBP）反应性T细胞，以及这种呈递是否被IL-12/IL-23 p40抗体阻断。干扰素（IFN）-γ处理的APC诱导MBP反应性T细胞的增殖。抗IL-12/IL-23 p40抗体阻断了这种增殖。这些结果支持并扩展了我们先前的观察，即星形胶质细胞和小胶质细胞产生IL-12/IL-23 p40。此外，我们表明，刺激的星形胶质细胞和小胶质细胞产生生物活性的IL-12 p70。由于IL-12和IL-23共享p40，我们想确定星形胶质细胞是否也表达IL-12 p35和IL-23 p19，因为小胶质细胞已经显示表达它们。星形胶质细胞组成型表达IL-12 p35 mRNA，刺激后表达IL-23 p19。因此，星形胶质细胞在炎症条件下表达IL-12/IL-23的所有亚基。它们将抗原呈递给致脑炎性T细胞的能力可以通过中和抗IL-12/IL-23 p40抗体来阻断。
Interleukin-12 (IL-12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1-type immune responses, has been attributed a prominent role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL-23, composed of the same p40 subunit as IL-12 and a unique p19 subunit, was shown to be involved in Th1 responses and EAE. We investigated whether astrocytes and microglia, CNS cells with antigen-presenting cell (APC) function can present antigen to myelin basic protein (MBP)-reactive T cells, and whether this presentation is blocked with antibodies against IL-12/IL-23p40. Interferon (IFN)-gamma-treated APC induced proliferation of MBP-reactive T cells. Anti-IL-12/IL-23p40 antibodies blocked this proliferation. These results support and extend our previous observation that astrocytes and microglia produce IL-12/IL-23p40. Moreover, we show that stimulated astrocytes and microglia produce biologically active IL-12p70. Because IL-12 and IL-23 share p40, we wanted to determine whether astrocytes also express IL-12p35 and IL-23p19, as microglia were already shown to express them. Astrocytes expressed IL-12p35 mRNA constitutively, and IL-23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions, express all subunits of IL-12/IL-23. Their ability to present antigen to encephalitogenic T cells can be blocked by neutralizing anti-IL-12/IL-23p40 antibodies.