Progesterone suppresses the mTOR pathway and promotes generation of induced regulatory T cells with increased stability.
Progesterone suppresses the mTOR pathway and promotes generation of induced regulatory T cells with increased stability.
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DOI：
10.1002/eji.201142317
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发表时间：
2012-10
影响因子：
5.4
通讯作者：
Kim, Chang H.
中科院分区：
文献类型：
--
作者：
Lee, Jee H.;Lydon, John P.;Kim, Chang H.
虽然诱导的FoxP 3 + T细胞（iTreg）是治疗炎症性疾病的有希望的细胞疗法，但利用体外制备的iTreg的局限性是它们在炎症条件下的稳定性低。孕酮（P4）是一种具有强效Treg诱导活性的免疫调节核激素。我们推断，孕酮的这种功能将用于产生具有高度抑制活性和改善的体内稳定性的iTlR。我们在体外用孕酮产生iTclad，并发现孕酮产生在炎症条件下高度稳定的iTclad。此外，P4-诱导的iTflu高度表达潜伏相关肽TGFβ1，并且在多种组织中有效调节炎症，而单独用TGFβ1诱导的对照iTflu不太稳定，并且在抑制炎症方面无效。孕酮在诱导具有改善的调节活性的iTlR中的功能与P4在抑制mTOR途径中的功能相关。此外，孕酮诱导FoxP 3 + T细胞的功能降低，但不完全废除核孕酮受体缺陷的T细胞，这表明核和非核孕酮受体参与介导的功能。我们的结论是，P4可用于产生在治疗组织炎症中具有高治疗潜力的iTlR。
While induced FoxP3+ T cells (iTregs) are promising cellular therapeutics to treat inflammatory diseases, a limitation in utilizing iTregs prepared in vitro is their low stability in inflammatory conditions. Progesterone (P4) is an immune regulatory nuclear hormone with a potent Treg induction activity. We reasoned that this function of progesterone would be utilized to generate iTregs with highly suppressive activity and improved stability in vivo. We generated iTregs with progesterone in vitro and found that progesterone generates iTregs that are highly stable in inflammatory conditions. Moreover, P4-induced iTregs highly express latency-associated peptide TGFβ1 and are efficient in regulating inflammation in multiple tissues, whereas control iTregs induced with TGFβ1 alone are less stable and ineffective in suppressing inflammation. The function of progesterone in inducing iTregs with improved regulatory activity is associated with the function of P4 in suppressing the mTOR pathway. Moreover, the function of progesterone in inducing FoxP3+ T cells is decreased but not completely abolished on nuclear progesterone receptor-deficient T cells, suggesting that both nuclear and non-nuclear progesterone receptors are involved in mediating the function. We conclude that P4 can be utilized to generate iTregs with a high therapeutic potential in treatment of tissue inflammation.
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影响因子：
32.4
作者：
Huber S;Gagliani N;Esplugues E;O'Connor W Jr;Huber FJ;Chaudhry A;Kamanaka M;Kobayashi Y;Booth CJ;Rudensky AY;Roncarolo MG;Battaglia M;Flavell RA
通讯作者：
Flavell RA
影响因子：
5.8
作者：
KONTULA, K;PAAVONEN, T;ANDERSSON, LC
通讯作者：
ANDERSSON, LC
影响因子：
9.1
作者：
Apostolou, Irina;Verginis, Panos;von Boehmer, Harald
通讯作者：
von Boehmer, Harald
1,25-二羟基维生素D3和IL-2结合抑制炎性细胞因子的T细胞产生，并促进表达CTLA-4和FOXP3的调节性T细胞的发育。
DOI：
10.4049/jimmunol.0803217
发表时间：
2009-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jeffery LE;Burke F;Mura M;Zheng Y;Qureshi OS;Hewison M;Walker LS;Lammas DA;Raza K;Sansom DM
通讯作者：
Sansom DM
DOI：
10.4049/jimmunol.0802535
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Haribhai D;Lin W;Edwards B;Ziegelbauer J;Salzman NH;Carlson MR;Li SH;Simpson PM;Chatila TA;Williams CB
通讯作者：
Williams CB