Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization
Golgi Phosphoprotein 2 Is a Novel Regulator of IL-12 Production and Macrophage Polarization
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高尔基磷蛋白 2 是 IL-12 产生和巨噬细胞极化的新型调节剂
DOI：
10.4049/jimmunol.1700897
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Ma Xiaojing
中科院分区：
文献类型：
--
作者：
Zhang Wei;Kim Hajeong;Lv Jiyang;Zhao Na;Ma Xiaojing
高尔基磷酸化蛋白2 （GOLPH2）是一种广泛表达的高尔基II型跨膜蛋白，参与了病毒感染、癌细胞增殖和转移等多种重要的生理和病理过程。然而，其生物学功能和机制，特别是在免疫系统中，仍然非常模糊。在本研究中，我们报告了B细胞淋巴瘤培养上清中GOLPH2的生化鉴定，并表明分泌的蛋白可以抑制树突状细胞（dc）产生IL-12和IL-12诱导的活化T细胞产生IFN-γ。进一步的分子分析表明，GOLPH2的il -12抑制活性是通过近端IL12p35启动子元件介导的，该元件涉及先前鉴定的转录抑制因子gc结合蛋白，该转录抑制因子在巨噬细胞吞噬凋亡细胞期间被诱导。随后，我们培育了全球golph2敲除小鼠，这些小鼠几乎没有发育异常，但与血清IL-12水平升高的野生型小鼠相比，它们更容易受到lps诱导的内毒素休克的影响。此外，我们发现GOLPH2在巨噬细胞向M2型极化中起调节作用。通过RNA测序对激活的野生型和GOLPH2缺陷DC的基因表达谱进行了全面分析，揭示了GOLPH2在炎症损伤期间可能调节DC功能的机制。我们对GOLPH2的功能研究有助于促进对这种新颖而有趣的分子的生物学和致病作用的科学理解，这种分子具有作为许多急慢性炎症疾病的诊断和预后标志物以及治疗靶点的巨大潜力。
Golgi phosphoprotein 2 (GOLPH2), a widely expressed Golgi type II transmembrane protein, has been implicated in several important physiological and pathological processes, including virus infections, cancer cell proliferation, and metastasis. However, its biological functions and mechanisms, particularly in the immune system, remain highly obscure. In this study, we report the biochemical identification of GOLPH2 from B cell lymphoma culture supernatant and show that the secreted protein could inhibit IL-12 production by dendritic cells (DCs) and IL-12–induced IFN-γ production by activated T cells. Further molecular analysis revealed that GOLPH2’s IL-12–inhibiting activity was mediated through a proximal IL12p35 promoter element involving a previously identified transcriptional repressor named GC-binding protein that is induced during phagocytosis of apoptotic cells by macrophages. We subsequently generated global golph2 knockout mice, which exhibited little developmental abnormality but were more susceptible to LPS-induced endotoxic shock than were wild-type mice with elevated serum IL-12 levels. Furthermore, we found that GOLPH2 played a regulatory role in macrophage polarization toward the M2 type. A comprehensive analysis of gene expression profiles of activated wild-type and GOLPH2-deficient DCs by RNA sequencing uncovered mechanistic insights into the way GOLPH2 potentially modulates DC function during inflammatory insults. Our functional study of GOLPH2 helps advance the scientific understanding of the biological and pathogenic roles of this novel and intriguing molecule with great potential as a diagnostic and prognostic marker as well as a therapeutic target in many acute and chronic inflammatory disorders.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
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影响因子：
5.6
作者：
Liu Y;Zou Z;Zhu B;Hu Z;Zeng P
通讯作者：
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影响因子：
50.3
作者：
Ye QH;Zhu WW;Zhang JB;Qin Y;Lu M;Lin GL;Guo L;Zhang B;Lin ZH;Roessler S;Forgues M;Jia HL;Lu L;Zhang XF;Lian BF;Xie L;Dong QZ;Tang ZY;Wang XW;Qin LX
通讯作者：
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影响因子：
64.8
作者：
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--
影响因子：
13.5
作者：
Riener, Marc-Oliver;Stenner, Frank;Kristiansen, Glen
通讯作者：
Kristiansen, Glen