Involvement of soluble scavenger receptor A in suppression of T cell activation in patients with chronic hepatitis B
Involvement of soluble scavenger receptor A in suppression of T cell activation in patients with chronic hepatitis B
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可溶性清道夫受体 A 参与抑制慢性乙型肝炎患者 T 细胞活化
DOI：
10.1186/s12865-015-0088-x
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发表时间：
2015-05-16
期刊：
影响因子：
3
通讯作者：
Zuo, Daming
中科院分区：
文献类型：
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作者：
Chen, Ying;Huang, Zuxiong;Zuo, Daming
清道夫受体A(Scavenger Receptor A，SRA)主要在吞噬细胞中表达，在宿主对入侵微生物的免疫防御中起着重要作用。我们先前的研究报告说，在乙肝病毒感染的患者中，SRA以可溶性形式存在。本研究检测了29例慢性乙型肝炎(CHB)患者、28例慢性乙肝病毒携带者(IT)、33例HBeAg阴性非活动性携带者(IC)和22例健康对照(HC)血清中的sSRA。我们进一步分析了检测到的可溶性SRA与炎症和血清病毒载量的相关性。此外，我们还研究了可溶性SRA在T细胞活化中的调节作用，特别是在CD8+T细胞对HBV肽的应答中的调节作用。CHB患者血清可溶性SRA水平与丙氨酸氨基转移酶水平呈负相关。我们还发现，在替比夫定治疗期间，血清SRA浓度降低。表达的sRa胞外区可抑制乙肝病毒核心肽刺激的T细胞产生干扰素-γ和肿瘤坏死因子-α，且其与T细胞的结合率在慢性乙肝患者高于慢性肝炎患者。此外，我们还观察到在重组SRA蛋白存在的情况下，抗CD3和CD28抗体刺激的原始人类T细胞活化和增殖减少。结论：我们测定了CHB患者不同阶段血清中可溶性SRA水平。SRA可能以可溶性形式抑制T细胞的增殖和活化。这些结果不仅揭示了CHB患者可溶性SRA以前未知的特征，而且也为了解SRA在T细胞激活中的作用提供了更广泛的理解。
BackgroundScavenger receptor A (SRA) is expressed predominantly in phagocytic cells playing an essential role in the host immune defense against invading microorganisms. Our previous study reported the presence of SRA in a soluble form in patients with infection of hepatitis B viruses (HBV). However, the association of soluble SRA with stages of HBV infection and the immune response induced by HBV is not fully determined.MethodsIn this study, we detected soluble SRA in serum from 29 chronic hepatitis B (CHB) patients, 28 chronic HBV carriers in the immune tolerant (IT) stage, 33 in the HBeAg-negative inactive carrier (IC) stage, and 22 healthy controls (HCs), respectively. We further analyzed the correlation of detected soluble SRA to inflammation and serum viral load. In addition, we investigated the regulatory role of soluble SRA in T cell activation, especially in CD8+T cell response to HBV peptide.ResultsWe demonstrated that Median levels of serum soluble SRA in CHB and IT patients were significantly higher than those of IC patients and HCs. Additionally, the concentrations of soluble SRA were negatively correlated with alanine transaminase levels in CHB patients. We also found that serum concentration of SRA was decreased during telbivudine treatment. Expressed SRA extracellular domain suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in CD8+T cells, and it bound to T cells in a higher frequency in CHB patients than in HCs. Furthermore, we observed that naïve human T cells stimulated by anti-CD3 and CD28 antibodies in the presence of the recombinant SRA protein had reduced activation and proliferation.ConclusionIn summary, we determined the level of soluble SRA in different stages of CHB patients. SRA might inhibit T cell proliferation and activation as a soluble form. These results not only revealed a previously unknown feature of soluble SRA in CHB patients but also provided broad understanding of SRA in T cell activation.