Association of the LILRA3 deletion with B-NHL and functional characterization of the immunostimulatory molecule.

Association of the LILRA3 deletion with B-NHL and functional characterization of the immunostimulatory molecule.
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LILRA3 缺失与 B-NHL 的关联以及免疫刺激分子的功能表征。

DOI:
10.1371/journal.pone.0081360
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Witte T
Witte T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Low HZ;Reuter S;Topperwien M;Dankenbrink N;Peest D;Kabalak G;Stripecke R;Schmidt RE;Matthias T;Witte T

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LILRA3是LILR家族中唯一可溶的成员。我们小组以前的研究表明,LILRA3基因6.7kb的缺失与MS和Sjögren综合征有关。免疫应答受损导致B-NHL的易感性,因此我们想要研究LILRA3的缺失是否也是B-NHL的危险因素,以及LILRA3的功能。我们发现B-非霍奇金淋巴瘤中LILRA3纯合子缺失的频率(6%)显著高于献血者(3%)(P = 0.03)。我们检测到荧光偶联的重组LILRA3与单核细胞和B细胞的结合。CFSE染色显示重组LILRA3可诱导CD8+T细胞和NK细胞的增殖。利用Transwell系统,我们证明了LILRA3刺激的淋巴细胞增殖是由单核细胞介导的,需要细胞接触和可溶性因子。ILRA3刺激细胞培养上清液中IL-6、IL-8、IL-1β和IL-10的分泌。我们认为,LILRA3是一种免疫刺激分子,其缺陷与B-NHL的发生频率较高有关。
LILRA3 is the sole soluble member of the LILR family. Previous studies from our group had shown that a 6.7 kb genetic deletion of LILRA3 is associated with MS and Sjögren’s syndrome. An impairment of the immune response leads to a predisposition for B-NHL, so we wanted to study whether the deletion of LILRA3 is also a risk factor for B-NHL, as well as the function of LILRA3. We discovered that the frequency of the homozygous LILRA3 deletion was significantly higher in B-NHL (6%) than in blood donors (3%) (P = 0.03). We detected binding of fluorochrome-conjugated recombinant LILRA3 to monocytes and B-cells. Incubation of PBMCs with recombinant LILRA3 induced proliferation of CD8+ T-cells and NK cells, as determined by CFSE staining. Using a transwell system, we demonstrated that LILRA3-stimulated lymphocyte proliferation was mediated by monocytes and required both cell contact and soluble factors. Secretion of IL-6, IL-8, IL-1β and IL-10 in the cell supernatant was stimulated by LILRA3. We conclude that LILRA3 is an immunostimulatory molecule, whose deficiency is associated with higher frequency of B-NHL.
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