Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease.
Upregulation of IFN-Inducible and Damage-Response Pathways in Chronic Graft-versus-Host Disease.
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DOI：
10.4049/jimmunol.1601054
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Gress RE
中科院分区：
文献类型：
--
作者：
Hakim FT;Memon S;Jin P;Imanguli MM;Wang H;Rehman N;Yan XY;Rose J;Mays JW;Dhamala S;Kapoor V;Telford W;Dickinson J;Davis S;Halverson D;Naik HB;Baird K;Fowler D;Stroncek D;Cowen EW;Pavletic SZ;Gress RE
虽然慢性移植物抗宿主病(CGVHD)是异基因移植的主要无复发并发症，但对其发病机制的了解有限。为了确定cGVHD光谱中的主要作用途径，我们分析了循环单核细胞中的基因表达，选择作为原位系统报告细胞。微阵列确定了两条相互关联的途径：(1)干扰素诱导基因和(2)细胞损伤的先天受体。通过多重RNA定量证实，与正常对照组和非CGVHD对照组相比，cGVHD单核细胞中多种干扰素诱导基因(影响淋巴细胞转运、分化和抗原提呈)同时上调。干扰素诱导的趋化因子在苔藓样和硬化性CGHVD血浆中均升高，并与CXCR3+淋巴细胞转运有关。此外，干扰素诱导基因CXCL10和TNFSF13B(BAFF)水平在基因水平和血浆水平上都相关，暗示干扰素诱导是cGVHD患者BAFF水平升高的一个因素。在第二个途径中，能够诱导I型干扰素的DAMP/PAMP受体基因上调。I型干扰素诱导的MxA在皮肤、粘膜和腺体中的表达与cGVHD活性成正比，在单核细胞中TLR和RIG-1受体基因的表达与I型干扰素诱导基因的上调有关。最后，在移植后的一系列分析中，干扰素诱导的和损伤反应基因在cGVHD开始时在单核细胞中上调，在苔藓样和硬化性cGVHD患者中随着治疗和缓解而下降。这种对干扰素诱导基因、血浆分析和组织免疫组织化学的连锁分析有力地支持了一个统一的假说，即通过对细胞损伤的先天反应诱导干扰素是cGVHD启动和持续的机制。
Although Chronic Graft-versus-Host Disease (CGVHD) is the primary non-relapse complication of allogeneic transplantation, understanding of its pathogenesis is limited. To identify the main operant pathways across the spectrum of CGVHD, we analyzed gene expression in circulating monocytes, chosen as in situ systemic reporter cells. Microarrays identified two interrelated pathways: (1) Interferon-inducible genes and (2) innate receptors for cellular damage. Corroborating these with multiplex RNA quantitation, we found that multiple IFN-inducible genes (affecting lymphocyte trafficking, differentiation and antigen presentation) were concurrently upregulated in CGVHD monocytes compared to normal and nonCGVHD controls. IFN-inducible chemokines were elevated in both lichenoid and sclerotic CGHVD plasma and linked to CXCR3+ lymphocyte trafficking. Furthermore, the IFN-inducible genes CXCL10 and TNFSF13B (BAFF) levels were correlated at both the gene and plasma levels, implicating IFN-induction as a factor in elevated BAFF levels in CGVHD. In the second pathway, DAMP/PAMP receptor genes capable of inducing Type I IFN were upregulated. Type I IFN-inducible MxA was expressed in proportion to CGVHD activity in skin, mucosa and glands, and expression of TLR and RIG-1 receptor genes correlated with upregulation of Type I IFN-inducible genes in monocytes. Finally, in serial analyses following transplant, IFN-inducible and damage-response genes were upregulated in monocytes at CGVHD onset and declined upon therapy and resolution in both lichenoid and sclerotic CGVHD patients. This interlocking analysis of IFN-inducible genes, plasma analytes and tissue immunohistochemistry strongly supports a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD.
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人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
DOI：
10.1038/nri3212
发表时间：
2012-05-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.8
作者：
Hamaki, T;Kami, M;Mutou, Y
通讯作者：
Mutou, Y
影响因子：
4.4
作者：
Harigai, Masayoshi;Kawamoto, Manabu;Miyasaka, Nobuyuki
通讯作者：
Miyasaka, Nobuyuki
影响因子：
20.3
作者：
Ehrchen, Jan;Steinmueller, Lars;Roth, Johannes
通讯作者：
Roth, Johannes