Herbal Components of a Novel Formula PSORI-CM02 Interdependently Suppress Allograft Rejection and Induce CD8+CD122+PD-1+ Regulatory T Cells.
Herbal Components of a Novel Formula PSORI-CM02 Interdependently Suppress Allograft Rejection and Induce CD8+CD122+PD-1+ Regulatory T Cells.
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新配方 PSORI-CM02 的草药成分可相互依赖性地抑制同种异体移植排斥并诱导 CD8 CD122 PD-1 调节性 T 细胞
DOI：
10.3389/fphar.2018.00088
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发表时间：
2018
影响因子：
5.6
通讯作者：
Dai Z
中科院分区：
文献类型：
--
作者：
Lu C;Liu H;Jin X;Chen Y;Liang CL;Qiu F;Dai Z
受体通常会排斥移植器官，因此需要免疫抑制治疗来防止排斥反应。在移植过程中，实现长期的同种异体移植物存活而无需持续的全身性免疫抑制是非常理想的，因为长期免疫抑制会导致各种副作用。因此，有必要寻找潜在副作用较小的药物。中药银屑灵（PSORI - CM01）是一种由七种天然草药组成的配方，已被用于治疗银屑病患者。在此，我们研究了一种“精简”配方PSORI - CM02，它仅由PSORI - CM01中的五种草药组成：莪术、赤芍、土茯苓、乌梅和肿节风。我们检测了PSORI - CM02是否会抑制同种免疫，发现PSORI - CM02显著抑制了小鼠皮肤同种异体移植物排斥反应，并减少了CD3 + T细胞在移植物中的浸润。有趣的是，去除任何一种单一草药成分都会使整个配方失去抑制作用，这表明这些草药成分是作为一个整体协同发挥作用的。此外，PSORI - CM02增加了受体小鼠中CD8 + CD122 + PD - 1 +调节性T细胞（Treg）的频率，而CD4 + FoxP3 + Tregs保持不变，而环孢素A（CsA）则降低了CD4 + FoxP3 + Treg的频率。PSORI - CM02还阻碍了移植后CD11c +树突状细胞（DC）的成熟。重要的是，PSORI - CM02诱导的CD8 + CD122 + PD - 1 + Tregs在抑制Rag - / -小鼠同种异体移植物排斥方面比对照Tregs更有效。另一方面，PSORI - CM02在体外抑制T细胞增殖，并降低其P70S6K和P50 / P65的磷酸化，这表明它抑制了mTOR和NFκB信号通路。它还增加了与CD8 + CD122 + PD - 1 + Tregs共培养的活化T细胞上清液中IL - 10的产生，同时降低了IFNγ水平。此外，高效液相色谱（HPLC）指纹图谱排除了PSORI - CM02含有CsA或雷帕霉素的可能性。PSORI - CM02也未在受体小鼠中引起任何疾病和毒性损伤。因此，我们证明了PSORI - CM02配方在无毒性的情况下抑制同种异体移植物排斥反应。
A recipient usually rejects a transplanted organ and thus needs immunosuppressive treatments to prevent rejection. Achieving long-term allograft survival without continuous global immunosuppression is highly desirable in transplantation as long-term immunosuppression causes various side effects. Therefore, it is necessary to search for medicine with potentially less side effects. Traditional Chinese medicine PSORI-CM01 (Yin Xie Ling), a formula with seven natural herbs, has been used to treat patients with psoriasis. Here, we investigated a “sharpened” formula, PSORI-CM02 consisting of only five herbs from PSORI-CM01: Curcumae rhizoma, Radix paeoniae rubra, Rhizoma smilacis glabrae, Mume fructus, and Sarcandrae herba. We examined whether or not PSORI-CM02 would suppress alloimmunity and found that PSORI-CM02 significantly inhibited murine skin allograft rejection and reduced graft-infiltration of CD3+ T cells. Interestingly, omitting any single herbal component rendered the whole formula ineffective in suppression, indicating that these herbal components exert their effects cooperatively as a whole. Moreover, PSORI-CM02 increased CD8+CD122+PD-1+ Treg frequency with CD4+FoxP3+ Tregs remaining unchanged in recipient mice, whereas CsA reduced CD4+FoxP3+ Treg frequency. PSORI-CM02 also hindered CD11c+ DC maturation posttransplantation. Importantly, PSORI-CM02-induced CD8+CD122+PD-1+ Tregs were more potent in suppression of allograft rejection in Rag-/- mice than control Tregs. On the other hand, PSORI-CM02 suppressed T cell proliferation in vitro and reduced their phosphorylation of P70S6K and P50/P65, suggesting that it inhibits both mTOR and NFκB signaling pathways. It also increased IL-10 production while reducing IFNγ level in the supernatant of activated T cells co-cultured with CD8+CD122+PD-1+ Tregs. Furthermore, HPLC fingerprinting ruled out that PSORI-CM02 contained CsA or rapamycin. PSORI-CM02 also did not cause any illness and toxic injury in recipient mice. Thus, we demonstrate that PSORI-CM02 formula suppresses allograft rejection without toxicity.
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影响因子：
2.9
作者：
Deng J;Yao D;Lu C;Wen Z;Yan Y;He Z;Wu H;Deng H
通讯作者：
Deng H
DOI：
10.1111/j.1600-6143.2012.04133.x
发表时间：
2012-09
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：
Aoyama A;Klarin D;Yamada Y;Boskovic S;Nadazdin O;Kawai K;Schoenfeld D;Madsen JC;Cosimi AB;Benichou G;Kawai T
通讯作者：
Kawai T
影响因子：
5.6
作者：
Han, Ling;Sun, Jing;Wei, Jian-an
通讯作者：
Wei, Jian-an
影响因子：
8.8
作者：
Dai, Z.;Zhang, S.;Li, X. C.
通讯作者：
Li, X. C.
DOI：
10.1111/j.1600-6143.2012.04120.x
发表时间：
2012-09
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：
Lerret NM;Houlihan JL;Kheradmand T;Pothoven KL;Zhang ZJ;Luo X
通讯作者：
Luo X