A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells.
A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells.
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DOI：
10.1038/s41467-017-01886-6
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发表时间：
2017-11-23
影响因子：
16.6
通讯作者：
Maizels RM
中科院分区：
文献类型：
--
作者：
Johnston CJC;Smyth DJ;Kodali RB;White MPJ;Harcus Y;Filbey KJ;Hewitson JP;Hinck CS;Ivens A;Kemter AM;Kildemoes AO;Le Bihan T;Soares DC;Anderton SM;Brenn T;Wigmore SJ;Woodcock HV;Chambers RC;Hinck AP;McSorley HJ;Maizels RM
寄生虫通过复杂的逃避机制对抗免疫排斥，包括激活宿主免疫抑制调节性T （Treg）细胞。小鼠寄生虫多回Heligmosomoides polygyrus可以通过分泌激活TGF-β信号传导的产物来扩大宿主Treg种群，但活性分子的身份尚不清楚。在这里，我们鉴定了一个多回H. TGF-β模拟物（Hp-TGM），它复制了TGF-β的生物学和功能特性，包括结合哺乳动物TGF-β受体和诱导小鼠和人类Foxp3+ Treg细胞。Hp-TGM与哺乳动物TGF-β或TGF-β家族的其他成员没有同源性，但它是补体控制蛋白超家族的成员。因此，我们的数据表明，通过趋同进化，寄生虫获得了一种具有细胞因子样功能的蛋白质，能够利用宿主体内的内源性免疫调节途径。多回Heligmosomoides polygyrus可以激活哺乳动物TGF-β信号通路，但其机制尚不清楚。在这里，作者鉴定并分离出一种多回H. TGF-β模拟物，它可以结合哺乳动物TGF-β受体亚基，激活Smad信号并产生可诱导的调节性T细胞。
Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host. Heligmosomoides polygyrus can activate mammalian TGF-β signalling pathways, but how it does so is not known. Here the authors identify and isolate a H. polygyrus TFG-β mimic that can bind both mammalian TGF-β receptor subunits, activate Smad signalling and generate inducible regulatory T cells.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
2.8
作者：
Benichou G;Yamada Y;Yun SH;Lin C;Fray M;Tocco G
通讯作者：
Tocco G
影响因子：
7.2
作者：
Hinck AP;Mueller TD;Springer TA
通讯作者：
Springer TA
DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM