Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function.
Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function.
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与半乳糖凝集素 1/CD7 通路功能受损相关的人肝同种异体移植排斥反应中功能失调的免疫调节
DOI：
10.1038/s41419-017-0220-3
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发表时间：
2018-02-20
影响因子：
9
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Wei S;Cao D;Liu Z;Li J;Wu H;Gong J;Liu Y;Wu Y
被排斥的同种异体移植患者的调节性T细胞无法控制应答性T细胞。半乳糖凝集素-1 （Gal1）通过结合CD7抑制应答T细胞。我们研究了同种异体肝移植排斥患者的免疫调节功能失调是否源于调节性t细胞Gal1表达和/或应答性t细胞CD7表达的降低。循环调节性T细胞和应答性T细胞分别来自31例急性排斥移植患者、85例缓解期移植患者和40例健康对照。CD7+和CD7−应答T细胞与调节性T细胞共培养，以评估调节性T细胞抑制功能。使用Gal1小干扰RNA沉默调节性t细胞Gal1。CD7+细胞百分比与AST、ALT、GGT水平呈负相关。CD7+应答T细胞和Gal1+调节性T细胞的比例在健康对照中高于缓解期移植患者，在急性排斥移植患者中最低。值得注意的是，CD7+应答t细胞对Gal1+调节性t细胞控制的易感性以相同的方式排名。在调节性T细胞中沉默Gal1表达降低了它们抑制CD7+（而不是CD7−）应答T细胞的能力。此外，健康对照中CD43+和CD45+应答T细胞的比例高于急性排斥移植患者。CD43共表达（而非CD45共表达）在CD7+应答T细胞上以gal1依赖的方式促进其凋亡。综上所述，同种异体肝移植排斥患者的免疫调节功能失调可部分归因于调节性t细胞Gal1表达降低和应答性t细胞CD7表达降低。急性排斥患者应答性t细胞CD43下调可能进一步导致应答性t细胞对调节性t细胞控制的反应性降低。
Regulatory T cells in rejected allograft patients display an inability to control responder T cells. Galectin-1 (Gal1) inhibits responder T cells through binding CD7. We investigated whether the dysfunctional immunoregulation in liver allograft rejection patients results from reduced regulatory T-cell Gal1 expression and/or responder T-cell CD7 expression. Circulating regulatory T cells and responder T cells were profiled from 31 acute rejection transplant patients, 85 transplant patients in remission, and 40 healthy controls. CD7+ and CD7− responder T cells were co-cultured with regulatory T cells to assess regulatory T-cell suppressor function. Gal1-small interfering RNA was used to silence regulatory T-cell Gal1. The CD7+ cell percentage was inversely correlated with AST, ALT, and GGT levels. The proportions of CD7+ responder T cells and Gal1+ regulatory T cells were higher in healthy controls than in transplant patients in remission and lowest in acute rejection transplant patients. Notably, CD7+ responder T-cell susceptibility to Gal1+ regulatory T-cell control was ranked in the same manner. Silencing Gal1 expression in regulatory T cells reduced their ability to suppress CD7+ (but not CD7−) responder T cells. Additionally, the proportions of CD43+ and CD45+ responder T cells were higher in healthy controls than in acute rejection transplant patients. CD43 co-expression (but not CD45 co-expression) on CD7+ responder T cells promoted their apoptosis in a Gal1-dependent manner. In sum, dysfunctional immunoregulation in liver allograft rejection patients can be partly attributed to reduced regulatory T-cell Gal1 expression and reduced responder T-cell CD7 expression. Responder T-cell CD43 downregulation in acute rejection patients may further contribute to reduced responder T-cell responsiveness to regulatory T-cell control.
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供体反应性T细胞的衰减可以使用调节性T细胞治疗有效控制同种异体移植的排斥。
DOI：
10.1111/ajt.12509
发表时间：
2014-01
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：
Lee K;Nguyen V;Lee KM;Kang SM;Tang Q
通讯作者：
Tang Q
DOI：
10.1111/ajt.13197
发表时间：
2015-01-01
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：
Kim, W R;Lake, J R;Kasiske, B L
通讯作者：
Kasiske, B L
DOI：
10.4049/jimmunol.0803833
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Pericolini E;Gabrielli E;Cenci E;De Jesus M;Bistoni F;Casadevall A;Vecchiarelli A
通讯作者：
Vecchiarelli A
影响因子：
20.3
作者：
Garin, Marina I.;Chu, Chung-Ching;Lechler, Robert I.
通讯作者：
Lechler, Robert I.
影响因子：
5.4
作者：
Moreau, Aurelie;Noble, Alistair;Lombardi, Giovanna
通讯作者：
Lombardi, Giovanna