CD24 hi CD27 + B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide
CD24 hi CD27 + B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide
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DOI：
10.1111/cea.12238
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发表时间：
2014-04-01
影响因子：
6.1
通讯作者：
Smits, H. H.
中科院分区：
文献类型：
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作者：
van der Vlugt, L. E. P. M.;Mlejnek, E.;Smits, H. H.
在实验模型中，调节性B细胞已被确定通过产生IL-10来强烈减少过敏性和自身免疫性炎症。最近，一些在自身免疫功能受损的人类调节性B细胞亚群已经被描述，但没有关于变应性哮喘的调节性B细胞的信息。目的探讨变应性哮喘中产生IL-10的b细胞亚群的频率和功能。方法对13例变应性哮喘患者和健康对照者的外周血B细胞进行不同调节性B细胞标志物的表达分析。接下来，用脂多糖（LPS）、CpG或通过B细胞受体激活B细胞，然后与内源性记忆CD4(+) T细胞和屋尘螨过敏原DerP1共培养。结果在LPS作用下，患者体内产生IL-10的B细胞数量较少，而通过B细胞受体或CpG激活的B细胞数量较少。进一步的解剖表明，只有CD24(hi)CD27(+) b细胞亚群的数量和IL-10的产生减少。在DerP1的作用下，来自患者的CD4(+) T细胞与lps诱导的总B细胞共培养产生的IL-10比来自对照组的类似培养少。这些结果与CD24(hi)CD27(+) B细胞负责诱导IL-10(+) CD4(+) T细胞的发现一致。综上所示，过敏性哮喘患者的CD24(hi)CD27(+) B细胞在LPS作用下产生较少的IL-10，导致T细胞对DerP1的IL-10诱导减弱，这可能在过敏性哮喘中发挥作用。
BackgroundRegulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma.ObjectiveIn this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated.MethodsIsolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4(+) T cells and house dust mite allergen DerP1.ResultsLower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24(hi)CD27(+) B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4(+) T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24(hi)CD27(+) B cells are responsible for the induction of IL-10(+) CD4(+) T cells.ConclusionsTaken together, these data indicate that CD24(hi)CD27(+) B cells from allergic asthma patients produce less IL-10 in response to LPS leading to a weaker IL-10 induction in T cells in response to DerP1, which may play a role in allergic asthma.