Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-β.
Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-β.
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DOI：
10.4049/jimmunol.1102389
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发表时间：
2012-01-15
期刊：
影响因子：
--
通讯作者：
Bryce PJ
中科院分区：
文献类型：
--
作者：
Ganeshan K;Bryce PJ
肥大细胞脱颗粒是过敏反应的标志，但肥大细胞也可以产生许多调节免疫的细胞因子。最近，CD 25+调节性T细胞（TCFs）已被证明可以抑制肥大细胞脱粒和过敏反应，但它们对细胞因子产生的影响仍然未知。在这里，我们表明，而不是抑制，TdR实际上增强肥大细胞的IL-6的生产。我们证明，虽然脱粒的抑制是OX 40/OX 40 L依赖性的，但IL-6的增强是由于TGFβ。有趣的是，我们的数据表明Treg衍生的TGFβ是表面结合的，因为相互作用是接触依赖性的，并且在上清液中检测不到TGFβ。单独的可溶性TGFβ1足以增强肥大细胞IL-6的产生，并且这些上清液足以促进TH 17偏斜，但来自Treg-肥大细胞培养物的上清液则不足以，这支持这是来自Treg的表面结合的TGFβ。有趣的是，IL-6产生的增加发生在基础上或响应于先天刺激（LPS或PGN）、适应性刺激（特异性抗原引起的IgE交联）和细胞因子活化（IL-33）。我们证明，TGFβ导致激活后IL-6的转录和从头合成增强，而不影响IL-6储存或mRNA稳定性。在体内，过继转移的TcR抑制肥大细胞依赖性过敏反应的食物过敏模型，但促进肠道IL-6和IL-17的生产。因此，我们的研究结果表明，TGFAP可以对肥大细胞产生不同的影响：通过OX 40/OX 40 L相互作用抑制脱粒，同时通过TGFβ促进IL-6。
Mast cell degranulation is a hallmark of allergic reactions but mast cells can also produce many cytokines that modulate immunity. Recently, CD25+ regulatory T cells (Tregs) have been shown to inhibit mast cell degranulation and anaphylaxis but their influence on cytokine production remained unknown. Here, we show that, rather than inhibit, Tregs actually enhance mast cell production of IL-6. We demonstrate that, while inhibition of degranulation was OX40/OX40L dependent, enhancement of IL-6 was due to TGFβ. Interestingly, our data demonstrates that the Treg-derived TGFβ was surface-bound, since the interaction was contact dependent and no TGFβ was detectable in the supernatant. Soluble TGFβ1 alone was sufficient to enhance mast cell IL-6 production and these supernatants were sufficient to promote TH17 skewing but those from Treg-mast cell cultures were not, supporting this being surface-bound TGFβ from the Tregs. Interestingly, the augmentation of IL-6 production occurred basally or in response to innate stimuli (LPS or PGN), adaptive stimuli (IgE crosslinking by specific antigen), and cytokine activation (IL-33). We demonstrate that TGFβ led to enhanced transcription and de novo synthesis of IL-6 upon activation, without affecting IL-6 storage or mRNA stability. In vivo, the adoptive transfer of Tregs inhibited mast cell dependent anaphylaxis in a model of food allergy but promoted intestinal IL-6 and IL-17 production. Consequently, our findings establish that Tregs can exert divergent influences upon mast cells: inhibiting degranulation via OX40/OX40L interactions while promoting IL-6 via TGFβ.
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DOI：
10.1111/j.1600-6143.2009.02755.x
发表时间：
2009-10
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
de Vries VC;Wasiuk A;Bennett KA;Benson MJ;Elgueta R;Waldschmidt TJ;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
4.4
作者：
Jalukar, SV;Hostager, BS;Bishop, GA
通讯作者：
Bishop, GA
影响因子：
32.4
作者：
Gri G;Piconese S;Frossi B;Manfroi V;Merluzzi S;Tripodo C;Viola A;Odom S;Rivera J;Colombo MP;Pucillo CE
通讯作者：
Pucillo CE
影响因子：
5.4
作者：
Davidson, Todd S.;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.
影响因子：
14.2
作者：
Li, XM;Schofield, BH;Sampson, HA
通讯作者：
Sampson, HA