Intrinsic hyporesponsiveness of invariant natural killer T cells precedes the onset of lupus.
Intrinsic hyporesponsiveness of invariant natural killer T cells precedes the onset of lupus.
复制标题
不变的自然杀伤 T 细胞的内在反应性低下先于狼疮发作。
DOI：
10.1111/cei.12079
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发表时间：
2013
影响因子：
4.6
通讯作者：
Singh,RR
中科院分区：
文献类型：
--
作者：
Yang,J-Q;Kim,PJ;Halder,RC;Singh,RR
Patients with systemic lupus erythematosus (SLE) display reduced numbers and functions of invariant natural killer T (iNK T) cells, which are restored upon treatment with corticosteroids and rituximab. It is unclear whether the iNK T cell insufficiency is a consequence of disease or is a primary abnormality that precedes the onset of disease. To address this, we analysed iNK T cell function at different stages of disease development using the genetically lupus-susceptible NZB × NZW F1(BWF1) model. We found that iNK T cellin-vivocytokine responses to an iNK T cell ligand α-galactosylceramide (α-GalCer) were lower in BWF1mice than in non-autoimmune BALB/c and major histocompatibility complex (MHC)-matched NZB × N/B10.PL F1mice, although iNK T cell numbers in the periphery were unchanged in BWF1mice compared to control mice. Such iNK T cell hyporesponsiveness in BWF1mice was detected at a young age long before the animals exhibited any sign of autoimmunity.In-vivoactivation of iNK T cells is known to transactivate other immune cells. Such transactivated T and B cell activation markers and/or cytokine responses were also lower in BWF1mice than in BALB/c controls. Finally, we show that iNK T cell responses were markedly deficient in the NZB parent but not in NZW parent of BWF1mice, suggesting that BWF1might inherit the iNK T cell defect from NZB mice. Thus, iNK T cells are functionally insufficient in lupus-prone BWF1mice. Such iNK T cell insufficiency precedes the onset of disease and may play a pathogenic role during early stages of disease development in SLE.
