Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.
Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.
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DOI：
10.1002/eji.201344284
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发表时间：
2014-07
影响因子：
5.4
通讯作者：
Ho LP
中科院分区：
文献类型：
--
作者：
Crawshaw A;Kendrick YR;McMichael AJ;Ho LP
结节病是一种多系统肉芽肿性疾病，其特征是辅助性T细胞1（Th 1）细胞的T细胞明显扩张。T细胞过度活跃的原因尚不清楚。我们假设，一种尚未确定的细胞类型产生的白细胞介素-10（IL-10）可能是有缺陷的，导致T细胞活性调节的丧失。聚焦于产生IL-10的单核细胞，我们首先发现从皮质类固醇初治的结节病患者（n = 51）的外周血中分离的单核细胞与对照组相比产生较少的IL-10，并且抑制T细胞增殖的能力较低。此外，单核细胞IL-10的产生与疾病活动评分呈负相关。由于已知不变的自然杀伤T（iNKT）细胞既与单核细胞相互作用，又在结节病患者中减少，因此我们询问iNKT特异性缺陷是否可能导致IL-10产生减少。我们发现，更多数量的循环iNKT细胞与更高的IL-10产生相关。此外，iNKT细胞在体外增强单核细胞IL-10的产生。结节病单核细胞与iNKT细胞共培养后，在CD 1d和细胞接触依赖性过程中，IL-10产生缺陷和T细胞抑制可以恢复。我们认为，结节病中iNKT细胞数量减少可能导致单核细胞IL-10产生受损和结节病中T细胞扩增不受抑制。这些发现为结节病的发病机制以及iNKT细胞和单核细胞之间的相互作用提供了新的见解。
Sarcoidosis is a multisystem granulomatous disorder characterized by marked T‐cell expansion of T helper 1 (Th1) cells. The cause of T‐cell overactivity is unknown. We hypothesized that interleukin‐10 (IL‐10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T‐cell activity. Focusing on IL‐10‐producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid‐naïve sarcoidosis patients (n = 51) produced less IL‐10 compared to controls, and were less able to suppress T‐cell proliferation. In addition, monocytic IL‐10 production correlated negatively with disease activity score. As invariant natural killer T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT‐specific defects might be responsible for this reduced IL‐10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL‐10 production. Moreover, iNKT cells enhanced monocytic IL‐10 production in vitro. Defective IL‐10 production and T‐cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d‐ and cell contact‐dependent process. We suggest that reduced iNKT‐cell numbers in sarcoidosis may lead to impaired monocytic IL‐10 production and unchecked T‐cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes.