关于红斑狼疮复杂的问题，免疫学家是这样解答的……

（注意，本文为同事尝试着翻译的，如有错误烦请指出，不胜感激。）

来源:弗吉尼亚理工大学

生物医学研究人员怀疑，一组特定的免疫细胞很有可能是导致晚期红斑狼疮患者病情恶化的源头，但直到现在他们还不能确定是否是免疫细胞导致的。不过，一个免疫学家通过带有红斑狼疮的小鼠做实验发现，事实上并不是这些细胞导致的。

多年来,生物医学研究人员，他们怀疑极大可能是一组特定的免疫细胞导致患者感染上狼疮，但直到现在他们还没有确定是它导致或者其它原因导致的。

弗吉尼亚理工大学的免疫学家已经发现这些细胞,称为血浆树突细胞——事实上,导致了小鼠出现狼疮。这一新发现，10月份发表在《免疫学杂志》上，这将对红斑狼疮的未来研究上具有极其重要的意义。

鑫罗的免疫学生物医学科学系的助理教授和病理学Virginia-Maryland兽医学院和她的同事建立在早期的研究显示,狼疮患者暴露于干扰素α,一种蛋白质释放的血浆树突细胞,称为髓和其他免疫细胞。红斑狼疮是一种自身免疫性疾病,可能导致慢性疲劳,关节痛、皮疹、发热、肾功能衰竭,甚至死亡。在美国，它估计会影响300万人左右。

“临床资料显示,狼疮患者基因表达中证明他们已经暴露于这种蛋白质中了,”罗说。”这表明这种蛋白质有致病作用——换句话说,它可以导致疾病。”

同样,以干扰素α为抗癌药物的患者有时患皮肤病,进一步支持了这一假说,这种蛋白质会导致狼疮。2013年,一个研究小组发现,消除了免疫细胞的小鼠红斑狼疮的症状会减少,而在2014年,另一个研究小组试着将这些细胞在老鼠患病的早期和晚期阶段就进行阻断。

“当研究人员发现在疾病早期把细胞阻断,对治疗疾病的效果真的很强大,但在进一步研究这一现象,我们在实验中发现,由于某种原因晚期狼疮的老鼠却并没有产生干扰素α,”罗说。“我们问自己,这些细胞是如何致病性如果他们没有生产这种致病蛋白质?”

罗和她的同事们使用新的细胞排序技术将从小鼠骨髓和其他细胞中把浆细胞样树突细胞高纯度分离出来。然后他们与弗吉尼亚理工学院生物复杂性的研究人员研究了孤立的细胞使用RNA（核糖核酸）序列。科学家罗伯特·Settlage数据分析核心主任和Saikumar Karyala,基因组学研究实验室的实验室经理,分析了样本。助理教授李歌的基因组学和生物信息学的作物和土壤环境科学在农业与生命科学学院,也有助于分析数据。

“我们回答了这个多年来人们一直想知道的问题:这些细胞真的会引发疾病吗?”罗说。“我们的数据强烈表明,已经携带有狼疮细胞的病人，将不会再衍生出其它的疾病，因为伤害已经造成。”

尽管浆细胞样树突细胞在5年或10年内可能会导致狼疮发病，但这并不是导致狼疮症状日益显露的主要因素。“我们相信这些细胞只是一个引发狼疮的导火线,但不会导致之后出现日益恶化或病情加剧的情况,”罗解释道。“他们认为：这不仅仅是他们的日常工作，也考虑到免疫细胞治疗法对于狼疮病人具有深远的临床意义。

研究人员还发现,他们可以运用相同的技术用来针对红斑狼疮的生物标记物进行早期检测。“我们可以推进这组数据调查，尽可能早期发现并找出能够让浆细胞样树突细胞改变在狼疮起到的作用,”美国二甲胂酸艾哈迈德说,生物医学科学系的主任和病理学和论文的合著者。“知道这些将会如何影响治疗的变化，对患者来说，也许有些为时过早了，但这些也仅是比较基础的科普。”

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以上文章转载均来自弗吉尼亚理工大学提供的材料。

以下为原文：

Xiaofeng Liao (left), a Ph.D. student in the Department of Biomedical Sciences and Pathobiology, and Xin Luo, an assistant professor of immunology, are co-authors on a paper about late-stage lupus in mice.

Credit: Virginia Tech

For years, biomedical researchers have suspected that a specific set of immune cells are responsible for causing disease in lupus patients, but until now they haven't known for sure one way or the other.

A Virginia Tech immunologist has found that these cells -- called plasmacytoid dendritic cells -- do not, in fact, contribute to late-stage lupus in mice. The discovery, published in October in the Journal of Immunology, has implications for the future of lupus research.

Xin Luo, assistant professor of immunology in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland College of Veterinary Medicine, and her colleagues built upon earlier research showing that lupus patients have been exposed to interferon alpha, a type of protein released by plasmacytoid dendritic cells -- known as pDCs -- and other immune cells. Lupus is an autoimmune disease that can cause chronic fatigue, joint pain, rash, fever, renal failure, and even death. It affects an estimated 3 million people in the United States.

"The clinical data show that patients with lupus have signatures in their gene expression demonstrating that they have been exposed to this protein," Luo said. "That suggests this protein has a pathogenic effect -- in other words, it can cause disease."

Similarly, patients who take interferon alpha as an anti-cancer drug sometimes develop lupus-like symptoms, further supporting the hypothesis that this protein causes lupus. In 2013, a research group found that removing the pDCs in mice reduced the symptoms of lupus, whereas in 2014, another research group removed these cells from mice in both the early and late stages of the disease.

"When the researchers removed the cell type early in the disease, they found that it was really strong at disease attenuation, but in studying this phenomenon further, we found in our experiments that for some reason mice with late-stage lupus didn't produce interferon alpha at all," Luo said. "We asked ourselves, 'How can these cells be pathogenic if they are not producing this pathogenic protein?' "

Luo and her colleagues used new cell-sorting technology to isolate pDCs at a high purity from the bone marrow in mice and separate them from other cells. They then partnered with researchers at the Biocomplexity Institute of Virginia Tech to study the isolated cells using RNA sequencing. Scientists Robert Settlage, director of the Data Analytics Core, and Saikumar Karyala, laboratory manager for the Genomics Research Laboratory, analyzed the samples. Song Li, assistant professor of genomics and bioinformatics in the Department of Crop and Soil Environmental Sciences in the College of Agriculture and Life Sciences, also helped to analyze the data.

"We answered the question that people have been wondering for many years: do these cells actually contribute to disease?" Luo said. "Our data strongly suggests that, in patients who already have lupus, pDCs don't contribute to disease anymore. The damage is already done."

Although pDCs may contribute to lupus five or 10 years before the onset of disease, they are not a factor after lupus symptoms develop. "We believe that these cells are only involved in the initiation of lupus, not the later exacerbation or progression of the disease," Luo explained. "This is very clinically relevant because many researchers are still thinking about targeting pDCs as a treatment for lupus patients, which may not work."

The researchers also found that they can use the same technology to search for early detection biomarkers for lupus. "We can move forward with this set of data to investigate possible early detection and figure out the role of the altered pDCs on lupus," said S. Ansar Ahmed, head of the Department of Biomedical Sciences and Pathobiology and paper co-author. "It's too early to know how these changes are going to affect treatment, but these are the building blocks."

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The above post is reprinted from materials provided by Virginia Tech. Note: Materials may be edited for content and length.