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BAFF/APRIL轴在虹鳟鱼病毒诱导的腹膜反应中起重要作用。

The BAFF / APRIL axis plays an important role in virus-induced peritoneal responses in rainbow trout.

作者信息

Soleto Irene, Abós Beatriz, Castro Rosario, González Lucia, Tafalla Carolina, Granja Aitor G

机构信息

Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.

Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.

出版信息

Fish Shellfish Immunol. 2017 May;64:210-217. doi: 10.1016/j.fsi.2017.03.023. Epub 2017 Mar 14.

DOI:10.1016/j.fsi.2017.03.023
PMID:28302579
Abstract

IgM B cells have been recently demonstrated to be key regulators of peritoneal inflammation in teleost, as a large number of them occupy the peritoneal cavity after 48 h of antigenic stimulation. Despite this, the number of studies addressing the mechanism through which this cell population expands and differentiates in response to stimuli has been scarcely addressed. Because the BAFF/APRIL axis is known to play a major role in B cell survival and differentiation in mammals, we hypothesized that it could be affected in the peritoneal cavity in response to an inflammatory stimulus. To verify this hypothesis, we studied how BAFF, APRIL and the fish-specific related cytokine BALM as well as their putative receptors are regulated in rainbow trout after intraperitoneal (i.p.) injection of viral hemorrhagic septicemia virus (VHSV). When the transcriptional analysis was performed in total cells from the peritoneum, we observed that VHSV provoked an up-regulation of both BAFF and BAFF receptor (BAFF-R) mRNA levels. However, when we examined how isolated peritoneal IgM B cells were transcriptionally affected by VHSV i.p. injection, we found that APRIL, BALM and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) were also up-regulated in response to the virus. IgM cells, on the other hand, only up-regulated BALM transcription in response to VHSV. Finally, to gain further insight on the role that these cytokines play in the peritoneum, we have studied their effect on the survival of peritoneal IgM B cells. This work demonstrates a key role for the BAFF/APRIL axis in the peritoneal inflammatory response and contributes to further understanding how IgM B cells are regulated at this specific peripheral site.

摘要

最近有研究表明,硬骨鱼体内的IgM B细胞是腹膜炎症的关键调节因子,因为大量此类细胞在抗原刺激48小时后会占据腹膜腔。尽管如此,针对这一细胞群体在受到刺激后扩增和分化机制的研究却很少。由于已知BAFF/APRIL轴在哺乳动物B细胞的存活和分化中起主要作用,我们推测它在腹膜腔中可能会因炎症刺激而受到影响。为了验证这一假设,我们研究了在虹鳟鱼腹腔注射病毒性出血性败血症病毒(VHSV)后,BAFF、APRIL和鱼类特异性相关细胞因子BALM以及它们的假定受体是如何被调节的。当对腹膜中的总细胞进行转录分析时,我们观察到VHSV引起了BAFF和BAFF受体(BAFF-R)mRNA水平的上调。然而,当我们检查腹腔注射VHSV后分离出的腹膜IgM B细胞在转录水平上受到的影响时,我们发现APRIL、BALM和跨膜激活剂、钙调蛋白和亲环素配体相互作用分子(TACI)也因病毒而上调。另一方面,IgM细胞仅在VHSV刺激下上调BALM的转录。最后,为了进一步深入了解这些细胞因子在腹膜中的作用,我们研究了它们对腹膜IgM B细胞存活的影响。这项工作证明了BAFF/APRIL轴在腹膜炎症反应中的关键作用,并有助于进一步理解IgM B细胞在这个特定外周部位是如何被调节的。

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