Haptoglobin deficiency facilitates the development of autoimmune inflammation
Haptoglobin deficiency facilitates the development of autoimmune inflammation
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DOI：
10.1002/eji.200939291
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发表时间：
2009-12-01
影响因子：
5.4
通讯作者：
Ceuppens, Jan L.
中科院分区：
文献类型：
--
作者：
Galicia, Georgina;Maes, Wim;Ceuppens, Jan L.
结合珠蛋白（HP）是由肝细胞响应IL-6而合成的急性期蛋白。HP已被证明可调节免疫应答并具有抗炎活性。为了分析HP在自身免疫性炎症中的作用，我们研究了用髓鞘少突胶质细胞糖蛋白肽（MOG（35-55））免疫Hp敲除小鼠（Hp（-/-））和同基因WT小鼠诱导的EAE的过程。Hp（-/-）小鼠患有更严重的疾病，与CNS中IL-17 A、IL-6和IFN-γ mRNA表达增加以及脊髓中细胞浸润密度增加相关。在恢复期，Hp（-/-）小鼠的CNS中持续存在显著较高数量的髓样DC、CD 8（+）细胞、IL-17（+）CD 4（+）和IFN-γ（+）CD 4（+）细胞。HP的缺乏影响了MOG 35 -55免疫后T细胞的引发和分化，因为响应于HP（-/-）T细胞的MOG刺激而产生的Th 2细胞因子水平降低。提示HP对中枢神经系统自身免疫性炎症具有调节和保护作用。
Haptoglobin (HP) is an acute phase protein synthesized by liver cells in response to IL-6. HP has been demonstrated to modulate the immune response and to have anti-inflammatory activities. To analyze HP's effect on autoimmune inflammation, we here studied the course of EAE induced by immunization of Hp knockout (Hp(-/-)) and syngeneic WT mice with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). Hp(-/-) mice suffered from a more severe disease that was associated with increased expression of IL-17A, IL-6, and IFN-gamma mRNA in the CNS and with a denser cellular infiltrate in the spinal cord. During the recovery phase, a significantly higher number of myeloid DC, CD8(+) cells, IL-17(+) CD4(+) and IFN-gamma(+) CD4(+) cells persisted in the CNS of Hp(-/-) mice. Absence of HP affected the priming and differentiation of T cells after MOG35-55 immunization, as levels of Th2 cytokines produced in response to MOG stimulation by Hp(-/-) T cells were reduced. These results suggest that HP plays a modulatory and protective role on autoimmune inflammation of the CNS.