Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice.
Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice.
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DOI：
10.1371/journal.pone.0139729
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Candotti F
中科院分区：
文献类型：
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作者：
Yokoyama T;Yoshizaki A;Simon KL;Kirby MR;Anderson SM;Candotti F
Wiskott-Aldrich综合征（WAS）是一种罕见的x连锁原发性免疫缺陷，以复发性感染、血小板减少、湿疹、恶性肿瘤和自身免疫的高发为特征。WAS自身免疫性并发症的细胞机制已被广泛研究；然而，它们仍然没有完全定义。我们研究了从Was基因敲除（WKO）小鼠中获得的产生il -10的CD19+CD1dhighCD5+ B细胞（CD1dhighCD5+ Breg）的特征，发现这些小鼠中的CD1dhighCD5+ Breg的数量明显低于野生型（WT）对照。此外，我们发现，与年龄匹配的WT对照小鼠相比，WKO CD1dhighCD5+ Breg细胞中il -10表达细胞的百分比明显随年龄减少。老年WKO小鼠的CD1dhighCD5+ Breg细胞在体外不抑制活化CD4+ T细胞产生炎性细胞因子。有趣的是，来自老年WKO小鼠的CD1dhighCD5+ Breg细胞表现出基础活化表型，这可能会阻止正常的细胞反应，其中包括IL-10的表达。这些缺陷可能有助于WAS患者随着年龄的增长对自身免疫的易感性。
The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg) obtained from Was gene knockout (WKO) mice and found that their numbers were significantly lower in these mice compared to wild type (WT) controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS.