Type 1 Interferon Gene Signature Promotes RBC Alloimmunization in a Lupus Mouse Model.
Type 1 Interferon Gene Signature Promotes RBC Alloimmunization in a Lupus Mouse Model.
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DOI：
10.3389/fimmu.2020.584254
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发表时间：
2020
影响因子：
7.3
通讯作者：
Gibb DR
中科院分区：
文献类型：
--
作者：
Lee JY;Madany E;El Kadi N;Pandya S;Ng K;Yamashita M;Jefferies CA;Gibb DR
红细胞（RBC）输血使接受者暴露于数百种不匹配的次要RBC抗原。这种暴露可导致产生同种抗体，促进临床显著的溶血事件。多项研究报告了自身免疫患者RBC同种免疫的频率增加。然而，自身免疫诱导的同种异体免疫的细胞和分子机制尚未报道。系统性红斑狼疮（SLE）患者具有高频率的同种异体免疫并表达1型干扰素（IFNα/β）基因特征。因此，我们利用降植烷诱导的狼疮小鼠模型来检验狼疮中的炎症促进RBC同种异体免疫的假设，并检查IFNα/β的潜在作用。腹腔注射降植烷（一种烃油）导致野生型（WT）小鼠产生自身抗体、肾小球肾炎和肺出血。降植烷治疗显著诱导血清IFNα和外周血和腹腔液细胞（包括炎性巨噬细胞）中多种干扰素刺激基因（ISG）的表达。输注表达KEL糖蛋白的同种异体RBC后，与未处理的小鼠相比，降植烷处理的WT小鼠产生显著升高水平的抗KEL IgM和抗KEL IgG。与WT小鼠相比，降植烷在缺乏IFNα/β受体（IFNAR 1-/-）或IFNα/β诱导性转录因子（IRF 3/7-/-）的小鼠中诱导的炎症细胞和细胞因子水平相当。然而，与WT小鼠相比，降植烷处理的IFNAR 1-/-和IRF 3/7-/-小鼠未能产生ISG，并且产生显著较低水平的输血诱导的抗KEL IgG。因此，降植烷诱导狼疮样表型以IFNα/β依赖性方式促进对KEL RBC抗原的同种免疫。据我们所知，这是第一次检查的分子机制，有助于红细胞同种异体免疫模型的自身免疫。这些结果保证了进一步研究IFNα/β在对其他RBC抗原的同种异体免疫中的作用以及IFNα/β基因特征对SLE患者同种异体免疫频率升高的贡献。
Red blood cell (RBC) transfusion exposes recipients to hundreds of unmatched minor RBC antigens. This exposure can lead to production of alloantibodies that promote clinically significant hemolytic events. Multiple studies have reported an increased frequency of RBC alloimmunization in patients with autoimmunity. However, cellular and molecular mechanisms that underlie autoimmunity-induced alloimmunization have not been reported. Patients with systemic lupus erythematosus (SLE) have a high frequency of alloimmunization and express a type 1 interferon (IFNα/β) gene signature. Thus, we utilized the pristane-induced lupus mouse model to test the hypothesis that inflammation in lupus promotes RBC alloimmunization, and to examine the potential role of IFNα/β. Intraperitoneal injection of pristane, a hydrocarbon oil, led to autoantibody production, glomerulonephritis, and pulmonary hemorrhage in wild type (WT) mice. Pristane treatment significantly induced serum IFNα and expression of multiple interferon-stimulated genes (ISGs) in peripheral blood and peritoneal fluid cells, including inflammatory macrophages. Following transfusion with allogeneic RBCs expressing the KEL glycoprotein, pristane-treated WT mice produced significantly elevated levels of anti-KEL IgM and anti-KEL IgG, compared to untreated mice. Pristane induced comparable levels of inflammatory cells and cytokines in mice lacking the IFNα/β receptor (IFNAR1–/–) or the IFNα/β-inducing transcriptions factors (IRF3/7–/–), compared to WT mice. However, pristane-treated IFNAR1–/– and IRF3/7–/– mice failed to produce ISGs and produced significantly lower levels of transfusion-induced anti-KEL IgG, compared to WT mice. Thus, pristane induction of a lupus-like phenotype promoted alloimmunization to the KEL RBC antigen in an IFNα/β-dependent manner. To our knowledge, this is the first examination of molecular mechanisms contributing to RBC alloimmunization in a model of autoimmunity. These results warrant further investigation of the role of IFNα/β in alloimmunization to other RBC antigens and the contribution of the IFNα/β gene signature to the elevated frequency of alloimmunization in patients with SLE.
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影响因子：
6.1
作者：
Holt, S;Donaldson, H;Burns, A
通讯作者：
Burns, A
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
桥接通道树突状细胞可诱导对输血的红细胞的免疫力。
DOI：
10.1084/jem.20151720
发表时间：
2016-05-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Calabro S;Gallman A;Gowthaman U;Liu D;Chen P;Liu J;Krishnaswamy JK;Nascimento MS;Xu L;Patel SR;Williams A;Tormey CA;Hod EA;Spitalnik SL;Zimring JC;Hendrickson JE;Stowell SR;Eisenbarth SC
通讯作者：
Eisenbarth SC
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
1.8
作者：
Hermida MDR;Malta R;de S Santos MDPC;Dos-Santos WLC
通讯作者：
Dos-Santos WLC