C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance.
C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance.
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DOI：
10.3389/fimmu.2018.00372
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发表时间：
2018
影响因子：
7.3
通讯作者：
Szalai AJ
中科院分区：
文献类型：
--
作者：
Jimenez RV;Wright TT;Jones NR;Wu J;Gibson AW;Szalai AJ
C-反应蛋白（CRP）是典型的急性期反应物，在炎症反应中，其血药浓度迅速增加数倍。最近的证据表明，CRP具有重要的生理作用，即使在低的基线水平，或在没有明显的炎症。例如，我们已经表明，人CRP通过将CD 4 + T细胞从TH 1向TH 2亚群转移来抑制CRP转基因小鼠中实验性自身免疫性脑脊髓炎（EAE）的进展。值得注意的是，该作用需要抑制性Fcγ受体IIB（FcγRIIB），但不需要高水平的人CRP。在此，我们试图确定CRP在EAE中的影响是否可以通过CRP作用于树突状细胞（DC;已知表达FcγRIIB的抗原呈递细胞）来解释。我们发现，CRP（50 μg/ml）降低了CD 11 c+骨髓来源的DC（BMDC）的产量，CRP（≥5 μg/ml）阻止了其II类主要组织相容性复合物和共刺激分子CD 86和CD 40的完全表达。CRP还降低了BMDC刺激体外抗原驱动的T细胞增殖的能力。重要的是，如果BMDC在小鼠FcγRIIB中存在遗传缺陷，则（i）CRP改变BMDC表面表型和损害T细胞增殖的能力被消除，（ii）CD 11 c驱动的人FCGR 2B转基因表达挽救了CRP效应。最后，在CD 11 c驱动的人Fe γRIIB表达的小鼠中，CRP对EAE的保护作用完全恢复。这些发现增加了越来越多的证据，即CRP即使在没有急性期反应的情况下也具有重要的生物学效应，即，CRP作为适应性免疫系统的紧张性抑制剂。CRP抑制DC发育、成熟和功能的能力暗示CRP在维持外周T细胞耐受中的作用。
C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE) in CRP transgenic mice by shifting CD4+ T cells away from the TH1 and toward the TH2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB), but did not require high levels of human CRP. Herein, we sought to determine if CRP’s influence in EAE might be explained by CRP acting on dendritic cells (DC; antigen presenting cells known to express FcγRIIB). We found that CRP (50 µg/ml) reduced the yield of CD11c+ bone marrow-derived DCs (BMDCs) and CRP (≥5 μg/ml) prevented their full expression of major histocompatibility complex class II and the co-stimulatory molecules CD86 and CD40. CRP also decreased the ability of BMDCs to stimulate antigen-driven proliferation of T cells in vitro. Importantly, if the BMDCs were genetically deficient in mouse FcγRIIB then (i) the ability of CRP to alter BMDC surface phenotype and impair T cell proliferation was ablated and (ii) CD11c-driven expression of a human FCGR2B transgene rescued the CRP effect. Lastly, the protective influence of CRP in EAE was fully restored in mice with CD11c-driven human FcγRIIB expression. These findings add to the growing evidence that CRP has important biological effects even in the absence of an acute phase response, i.e., CRP acts as a tonic suppressor of the adaptive immune system. The ability of CRP to suppress development, maturation, and function of DCs implicates CRP in the maintenance of peripheral T cell tolerance.
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影响因子：
10.1
作者：
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