B‐cell‐derived IL‐10 does not vitally contribute to the clinical course of glomerulonephritis
B‐cell‐derived IL‐10 does not vitally contribute to the clinical course of glomerulonephritis
复制标题
Bâcellâ 源性 ILâ10 对肾小球肾炎的临床病程没有重要影响
DOI：
10.1002/eji.201343842
复制
发表时间：
2014
影响因子：
5.4
通讯作者：
Steinmetz OM
中科院分区：
文献类型：
--
作者：
Kluger MA;Ostmann A;Luig M;Meyer MC;Goerke B;Paust HJ;Meyer-Schwesinger C;Stahl RA;Panzer U;Tiegs G;Steinmetz OM
IL - 10 -分泌调节性B细胞被认为是炎症的负介质。然而，它们对免疫介导疾病的影响需要进一步研究。我们最近发现，在月牙性肾小球肾炎（GN）期间，分泌IL - 10的B细胞浸润肾脏。因此，鉴于越来越多地使用B细胞消耗疗法的潜在风险，我们研究了B细胞来源的IL - 10的功能。然而，在肾毒性肾炎模型中，缺乏B细胞产生IL - 10并不影响急性或适应性介导的进行性肾损伤的肾功能和组织学损害。在缺乏B细胞源性IL - 10的小鼠中，除了巨噬细胞增加外，肾白细胞浸润和细胞因子表达相似。通过细胞因子产生、白细胞组成、增殖和激活来评估的全身免疫反应难以区分，而在缺乏B细胞产生的IL - 10的情况下，Ag特异性IgG的产生和肾沉积轻度受损。重要的是，对全身和肾脏调节性T细胞的详细分析显示，携带IL - 10缺陷B细胞的肾病小鼠和WT对照组之间没有任何差异。最后，对报告小鼠的研究表明，B细胞只是全身性IL - 10的一个次要来源。总之，我们的数据显示，内源性B细胞来源的IL - 10在月牙状GN肾毒性肾炎模型中不起主要作用。
IL‐10‐secreting regulatory B cells have been postulated as negative mediators of inflammation. However, their impact on immune‐mediated diseases requires further investigation. We recently found that IL‐10‐secreting B cells infiltrate the kidney during crescentic glomerulonephritis (GN). We therefore studied the function of B‐cell‐derived IL‐10 in light of the potential risks associated with increasingly used B‐cell depleting therapies. Lack of IL‐10 production by B cells, however, did not influence acute or adaptively mediated progressive renal injury in terms of renal function and histological damage in the nephrotoxic nephritis model of GN. Renal leukocyte infiltration and cytokine expression were similar apart from increased macrophages in mice lacking B‐cell‐derived IL‐10. Systemic immune responses as assessed by cytokine production, leukocyte composition, proliferation, and activation were indistinguishable, while production and renal deposition of Ag‐specific IgG were mildly impaired in the absence of B‐cell‐produced IL‐10. Importantly, detailed analysis of systemic and renal regulatory T cells did not show any differences between nephritic mice bearing IL‐10‐deficient B cells and WT controls. Finally, studies in reporter mice revealed that B cells are only a minor source of systemic IL‐10. In summary, our data reveal that endogenous B‐cell‐derived IL‐10 does not play a major role in the nephrotoxic nephritis model of crescentic GN.