IL-7 promotes T(H)1 development and serum IL-7 predicts clinical response to interferon-β in multiple sclerosis.
IL-7 promotes T(H)1 development and serum IL-7 predicts clinical response to interferon-β in multiple sclerosis.
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DOI：
10.1126/scitranslmed.3002400
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发表时间：
2011-07-27
影响因子：
17.1
通讯作者：
Lin JC
中科院分区：
文献类型：
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作者：
Lee LF;Axtell R;Tu GH;Logronio K;Dilley J;Yu J;Rickert M;Han B;Evering W;Walker MG;Shi J;de Jong BA;Killestein J;Polman CH;Steinman L;Lin JC
白细胞介素-7受体α链（IL-7 R α）基因被确定为多发性硬化症（MS）的最高非主要组织相容性复合体连锁风险基因座。最近，我们发现T辅助细胞1（TH 1）驱动的MS形式对干扰素-β（IFN-β）治疗表现出良好的临床反应，而不是TH 17驱动的MS形式。我们现在证明，高血清水平的IL-7，特别是当与低水平的IL-17 F配对时，预测对IFN-β的反应性，因此预测MS的TH 1驱动亚型。我们还表明，尽管IL-7信号传导对于TH 17细胞的诱导或扩增既不是必需的也不是充分的，但IL-7可以极大地增强人和小鼠TH 1细胞的分化。单独的IL-7足以在不存在IL-12或其它细胞因子的情况下诱导人TH 1分化。此外，靶向IL-7/IL-7 R α在实验性自身免疫性脑脊髓炎（EAE）（MS的小鼠模型）中是有益的。在瘫痪发作之前或之后用IL-7 R α阻断抗体治疗的小鼠表现出EAE的临床体征减少，外周幼稚和活化T细胞减少，而中枢记忆T细胞、调节性T细胞、B细胞和自然杀伤细胞群在很大程度上幸免。IL-7 R α抗体治疗显著减少EAE小鼠中枢神经系统的淋巴细胞浸润。因此，高IL-7血清谱可能意味着TH 1驱动的MS形式，并可能预测接受IFN-β治疗的MS患者的结局。IL-7和IL-7 R α通路的阻断可能对MS和其他自身免疫性疾病具有治疗潜力。
The interleukin-7 receptor α chain (IL-7Rα) gene was identified as a top non–major histocompatibility complex–linked risk locus for multiple sclerosis (MS). Recently, we showed that a T helper 1 (TH1)–driven, but not a TH17-driven, form of MS exhibited a good clinical response to interferon-β (IFN-β) therapy. We now demonstrate that high serum levels of IL-7, particularly when paired with low levels of IL-17F, predict responsiveness to IFN-β and hence a TH1-driven subtype of MS. We also show that although IL-7 signaling is neither necessary nor sufficient for the induction or expansion of TH17 cells, IL-7 can greatly enhance both human and mouse TH1 cell differentiation. IL-7 alone is sufficient to induce human TH1 differentiation in the absence of IL-12 or other cytokines. Furthermore, targeting IL-7/IL-7Rα is beneficial in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Mice treated with IL-7Rα–blocking antibodies before or after onset of paralysis exhibited reduced clinical signs of EAE, with reduction in peripheral naïve and activated T cells, whereas central memory T, regulatory T, B, and natural killer cell populations were largely spared. IL-7Rα antibody treatment markedly reduced lymphocyte infiltration into the central nervous system in mice with EAE. Thus, a serum profile of high IL-7 may signify a TH1-driven form of MS and may predict outcome in MS patients undergoing IFN-β therapy. Blockade of IL-7 and the IL-7Rα pathway may have therapeutic potential in MS and other autoimmune diseases.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.8
作者：
Lundmark, Frida;Duvefelt, Kristina;Hillert, Jan
通讯作者：
Hillert, Jan
影响因子：
3.3
作者：
Bielekova, B;Muraro, PA;Martin, R
通讯作者：
Martin, R
影响因子：
8
作者：
通讯作者：
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