IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition.
IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition.
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DOI：
10.1084/jem.20080159
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发表时间：
2008-07-07
期刊：
影响因子：
--
通讯作者：
Segal BM
中科院分区：
文献类型：
--
作者：
Kroenke MA;Carlson TJ;Andjelkovic AV;Segal BM
白细胞介素（IL）-12p40家族细胞因子在实验性自身免疫性脑脊髓炎（EAE）的发生发展中起着关键作用。然而，IL-12和IL-23对致病过程的相对贡献仍有待阐明。在这里，我们表明，在IL-12 p70或IL-23的存在下，未定型的髓鞘反应性T细胞的激活赋予致脑性。将IL-12 p70或IL-23极化的T细胞连续转移到幼稚同基因宿主中导致两组之间临床上无法区分的上行性麻痹。然而，中枢神经系统（CNS）组织的组织学和逆转录-聚合酶链反应分析显示不同的组织病理学特征和免疫概况。IL-12 p70驱动的疾病的特征在于巨噬细胞丰富的浸润和显著的NOS 2上调，而中性粒细胞和粒细胞集落刺激因子（CSF）在IL-23驱动的病变中是显著的。单核细胞吸引趋化因子CXCL 9、10和11在注射IL-12 p70调节的T细胞的小鼠的CNS中优先表达，而嗜中性粒细胞吸引趋化因子CXCL 1和CXCL 2在给予IL-23调节的T细胞的小鼠的CNS中上调。用抗IL-17或抗粒细胞/巨噬细胞-CSF治疗抑制由IL-23极化的细胞而不是IL-12 p70极化的细胞转移诱导的EAE。这些发现表明，自身免疫可以通过不同的效应群体介导，这些效应群体使用不同的免疫途径来实现相似的临床结果。
The interleukin (IL)-12p40 family of cytokines plays a critical role in the development of experimental autoimmune encephalomyelitis (EAE). However, the relative contributions of IL-12 and IL-23 to the pathogenic process remain to be elucidated. Here, we show that activation of uncommitted myelin-reactive T cells in the presence of either IL-12p70 or IL-23 confers encephalogenicity. Adoptive transfer of either IL-12p70– or IL-23–polarized T cells into naive syngeneic hosts resulted in an ascending paralysis that was clinically indistinguishable between the two groups. However, histological and reverse transcription–polymerase chain reaction analysis of central nervous system (CNS) tissues revealed distinct histopathological features and immune profiles. IL-12p70–driven disease was characterized by macrophage-rich infiltrates and prominent NOS2 up-regulation, whereas neutrophils and granulocyte–colony-stimulating factor (CSF) were prominent in IL-23–driven lesions. The monocyte-attracting chemokines CXCL9, 10, and 11 were preferentially expressed in the CNS of mice injected with IL-12p70–modulated T cells, whereas the neutrophil-attracting chemokines CXCL1 and CXCL2 were up-regulated in the CNS of mice given IL-23–modulated T cells. Treatment with anti–IL-17 or anti–granulocyte/macrophage-CSF inhibited EAE induced by transfer of IL-23–polarized, but not IL-12p70–polarized, cells. These findings indicate that autoimmunity can be mediated by distinct effector populations that use disparate immunological pathways to achieve a similar clinical outcome.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
3.3
作者：
Moldovan, IR;Rudick, RA;Pelfrey, CM
通讯作者：
Pelfrey, CM
影响因子：
6
作者：
Abromson-Leeman, S;Bronson, R;Dorf, M
通讯作者：
Dorf, M
DOI：
10.1084/jem.187.4.537
发表时间：
1998-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Segal BM;Dwyer BK;Shevach EM
通讯作者：
Shevach EM