Defective expression and function of the leukocyte associated Ig-like receptor 1 in B lymphocytes from systemic lupus erythematosus patients.
Defective expression and function of the leukocyte associated Ig-like receptor 1 in B lymphocytes from systemic lupus erythematosus patients.
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DOI：
10.1371/journal.pone.0031903
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Poggi A
中科院分区：
文献类型：
--
作者：
Colombo BM;Canevali P;Magnani O;Rossi E;Puppo F;Zocchi MR;Poggi A
系统性红斑狼疮（SLE）的特征是产生大量自身抗体和B细胞功能失调。白细胞相关免疫球蛋白（IG）样受体（LAIR）1是属于IG超家族的跨膜分子，其结合不同类型的胶原。本研究检测了SLE患者B淋巴细胞LAIR 1的表达及其功能。采用免疫荧光法检测了54例SLE、24例混合性结缔组织病（MCTD）、20例系统性硬化症（SSc）、14例类风湿性关节炎（RA）和40例性别和年龄匹配的健康献血员（HD）外周血B淋巴细胞中LAIR 1的表达。通过ELISA和TransAM测定评估了通过特异性单克隆抗体、胶原或来自反应性淋巴结或骨髓的产生胶原的间充质基质细胞连接LAIR 1对美洲商陆有丝分裂原和B细胞受体（BCR）介导的NF-κ B活化的IG产生的影响。与HD患者相比，SLE和MCTD患者中LAIR 1表达缺失或表达减少的CD 20 + B淋巴细胞百分比显著增加，但在SSc或RA患者中未增加。LAIR 1表达的下调不依赖于皮质类固醇治疗。有趣的是，在B细胞上LAIR 1表达低的SLE患者中，LAIR 1与胶原或产生胶原的间充质基质细胞的结合对IG产生的抑制信号较低。此外，SLE患者中BCR和LAIR 1共同参与时NF-kB p65亚基活化的抑制程度低于HD患者。我们的研究结果表明SLE B淋巴细胞中LAIR 1的表达和功能缺陷，可能导致B淋巴细胞行为控制的改变。
Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20+ B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior.
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影响因子：
5.4
作者：
Jiang, Lei;Barclay, A. Neil
通讯作者：
Barclay, A. Neil
影响因子：
4.4
作者：
Horton, Holly M.;Chu, Seung Y.;Szymkowski, David E.
通讯作者：
Szymkowski, David E.
影响因子：
4.4
作者：
Lebbink, Robert Jan;van den Berg, Maaike C. W.;Meyaard, Linde
通讯作者：
Meyaard, Linde
影响因子：
4.4
作者：
Poggi, A;Tomasello, E;Moretta, L
通讯作者：
Moretta, L
DOI：
10.3324/haematol.2010.031633
发表时间：
2011-01-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Musso, Alessandra;Zocchi, Maria Raffaella;Poggi, Alessandro
通讯作者：
Poggi, Alessandro