The Immunosuppressant Protosappanin A Promotes Dendritic Cell-Mediated Expansion of Alloantigen-Specific Tregs and Prolongs Allograft Survival in Rats.
The Immunosuppressant Protosappanin A Promotes Dendritic Cell-Mediated Expansion of Alloantigen-Specific Tregs and Prolongs Allograft Survival in Rats.
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DOI：
10.1371/journal.pone.0066336
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Zhang M;Zhang S;Wu J;Sun Y;Li L;Du W;Liu J;Hou J;Yu B
原苏木素A（Protosappanin A，PrA）是中药云实（Caesalpinia cerean L.）的一种免疫抑制成分，可能通过损害抗原提呈细胞（antigen presenting cells，APC）的功能而抑制大鼠心脏移植物的存活。我们研究了PrA对树突状细胞（DCs）成熟和功能的影响，树突状细胞是一种有效的APC，以及介导PrA免疫抑制活性的下游细胞-细胞和细胞内信号传导途径。PrA抑制LPS刺激的Wistar大鼠DCs体外成熟，表现为共刺激分子（CD 80和CD 86）表达减少以及TLR 4和NF-κB（抗原识别的两个关键信号组分）表达减少。PrA还可促进DC释放IL-10，减少IL-12，但对TGF-β的产生无影响。在混合培养中，用PrA预处理的Wistar DC损害了Sprague道利（SD）大鼠T细胞的增殖，同时促进SD大鼠CD 4 + CD 25+调节性T细胞（T细胞）的扩增。口服PrA治疗和输注PrA预处理的Wistar DC均延长了心脏同种异体移植物存活（Wistar供体，SD受体）和扩增的受体CD 4 + CD 25 + Foxp 3 + T细胞。供体脾细胞，而不是来自第三大鼠品系（DA）的脾细胞，支持受体CD 4 + CD 25 + Foxp 3 + T细胞的扩增并抑制受体T细胞增殖。我们的结论是，PrA触发的致耐受性的状态，允许诱导同种异体抗原特异性Tclase和同种异体移植排斥反应的抑制在体内的DC。
Protosappanin A (PrA), an immunosuppressive ingredient of the medicinal herb Caesalpinia sappan L, prolongs heart allograft survival in rats, possibly by impairing the function of antigen-presenting cells (APCs). We examined the effects of PrA on the maturation and function of dendritic cells (DCs), a potent class of APCs, and the downstream cell–cell and intracellular signaling pathways mediating the immunosuppressive activity of PrA. PrA inhibited LPS-stimulated maturation of Wistar rat DCs in vitro as reflected by reduced expression of costimulatory molecules (CD80 and CD86) and reduced expression of TLR4 and NF-κB, two critical signaling components for antigen recognition. PrA also enhanced the release of IL-10 and decreased the release of IL-12 from DCs, but had no effect on the production of TGF-ß. In mixed cultures, Wistar DCs pretreated with PrA impaired the proliferation of Sprague Dawley (SD) rat T cells while promoting the expansion of SD rat CD4+CD25+ regulatory T cells (Tregs). Both oral PrA treatment and infusion of PrA-pretreated Wistar DCs prolonged cardiac allograft survival (Wistar donor, SD recipient) and expanded recipient CD4+CD25+Foxp3+ Tregs. Donor spleen cells, but not spleen cells from a third rat strain (DA), supported the expansion of recipient CD4+CD25+Foxp3+ Tregs and suppressed recipient T cell proliferation. We conclude that PrA triggers a tolerogenic state in DCs that allows for the induction of alloantigen-specific Tregs and the suppression of allograft rejection in vivo.
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影响因子：
8.8
作者：
Pêche, H;Trinité, B;Cuturi, MC
通讯作者：
Cuturi, MC
DOI：
10.4049/jimmunol.0903412
发表时间：
2010-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Caretto D;Katzman SD;Villarino AV;Gallo E;Abbas AK
通讯作者：
Abbas AK
影响因子：
3.1
作者：
Braudeau, Cecile;Racape, Maud;Brouard, Sophie
通讯作者：
Brouard, Sophie
影响因子：
5.5
作者：
Hattori, Takaaki;Saban, Daniel R.;Dana, Reza
通讯作者：
Dana, Reza
影响因子：
4.4
作者：
Bonham, CA;Peng, LS;Lu, L
通讯作者：
Lu, L