Inactivation of the KSRP gene modifies collagen antibody induced arthritis
Inactivation of the KSRP gene modifies collagen antibody induced arthritis
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DOI：
10.1016/j.molimm.2017.05.003
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发表时间：
2017-07-01
影响因子：
3.6
通讯作者：
Pautz, Andrea
中科院分区：
文献类型：
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作者：
Kaefer, Rudolf;Schrick, Katharina;Pautz, Andrea
KH型剪接调节蛋白（KSRP）是一种核酸结合蛋白，其负调节编码免疫相关蛋白的许多mRNA种类的稳定性和/或可翻译性。由于KSRP在T、B细胞、中性粒细胞、巨噬细胞和树突状细胞等免疫细胞中均有表达，为了分析其在自身免疫性疾病发生发展中的重要作用，我们选择了胶原抗体诱导的关节炎（CAIA）作为自身免疫性疾病小鼠模型，其中中性粒细胞和巨噬细胞构成了主要的效应细胞群。我们比较了野生型（WT）和KSRP-/-小鼠中的关节炎诱导，并取爪进行组织切片和qPCR分析。流式细胞仪检测脾脏免疫细胞的频率。通过流式细胞仪珠阵列分析（CBA）测定脾细胞上清液中的细胞因子水平。在CAIA诱导后，我们意外地在WT动物中观察到比KSRP-/-小鼠更强的爪肿胀。因此，KSRP-/-动物的爪切片的组织学染色显示，与WT动物相比，关节中浸润免疫细胞的频率低得多。此外，CAIA治疗导致KSRP-/-小鼠关节中几种炎性因子（如CXCL-1、iNOS、TNF-α和S100 A8）以及免疫细胞标记基因（例如LFA-1、CD 68、Ly 6 G）的表达降低。在细胞因子水平上，与WT样品相比，KSRP-/-小鼠的脾细胞中IFN-γ的产生增加。
The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted to analyze its importance for the development of autoimmune diseases.We chose collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease mouse model in which neutrophils and macrophages constitute the main effector cell populations. We compared arthritis induction in wild type (WT) and KSRP-/- mice and paws were taken for histological sections and qPCR analysis. Furthermore, we determined the frequencies of spleen immune cells by flow cytometry. Cytokine levels in spleen cell supernatants were determined by cytometric bead array analyses (CBA).After CAIA induction we unexpectedly observed in WT animals much stronger swelling of the paws than in KSRP-/- mice. In accordance, histological staining of paw sections of KSRP-/- animals revealed much lower frequencies of infiltrating immune cells in the joints compared to WT animals. Furthermore, CAIA-treatment resulted in reduced expression of several inflammatory factors (like CXCL-1, iNOS, TNF-alpha and S100A8) as well as immune cell marker genes (e.g. LFA-1, CD68, Ly6G) in the joints of KSRP-/- mice.Spleen cells of KSRP-/- mice showed lower frequencies of myeloid cells. On cytokine level IFN-y production was increased in spleen cells of KSRP-/- mice compared to WT samples.These data surprisingly suggest that the absence of KSRP protects against the induction of inflammatory arthritis.