The receptor tyrosine kinase MerTK regulates dendritic cell production of BAFF.
The receptor tyrosine kinase MerTK regulates dendritic cell production of BAFF.
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DOI：
10.1080/08916930802668586
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发表时间：
2009-03
期刊：
影响因子：
3.5
通讯作者：
Matsushima GK
中科院分区：
文献类型：
--
作者：
Gohlke PR;Williams JC;Vilen BJ;Dillon SR;Tisch R;Matsushima GK
MerTK受体酪氨酸激酶是树突状细胞功能的重要负调节因子，并且是体内预防B细胞自身免疫所必需的。然而，目前尚不清楚MerTK功能的这两个方面之间是否存在因果关系。我们试图确定缺乏MerTK的小鼠（mertk−/−小鼠）的树突状细胞是否具有可能有助于B细胞自身免疫发展的特征。具体来说，我们发现mertk−/−小鼠的脾脏树突状细胞数量增加，并且这个群体中分泌关键的B细胞促生存因子B细胞活化因子（BAFF）的细胞比例增加。在mertk−/−骨髓来源的树突状细胞（BMDC）群体中也检测到BAFF分泌细胞数量增加。这在静息BMDC和用脂多糖（LPS）刺激或用外源性凋亡细胞处理的BMDC中均观察到。我们还发现，树突状细胞一般对共培养的静息B细胞具有促存活作用。然而，尽管含有更多的BAFF分泌细胞，mertk−/− BMDC在促进B细胞存活方面并不上级C57 BL/6或baff-deficient BMDC。此外，使用诱饵受体，我们表明，树突状细胞可以促进B细胞的生存和自身免疫，通过BAFF和APRIL的独立机制。
The MerTK receptor tyrosine kinase is an important negative regulator of dendritic cell function and is required to prevent B cell autoimmunity in vivo. It is not currently known however, if any causal relationship exists between these two aspects of MerTK function. We sought to determine if dendritic cells from mice lacking MerTK (mertk−/− mice) have characteristics that may aid in the development of B cell autoimmunity. Specifically, we found that mertk−/− mice contain an elevated number of splenic dendritic cells, and this population contains an elevated proportion of cells secreting the critical B cell pro-survival factor, B cell activating factor (BAFF). Elevated numbers of BAFF-secreting cells were also detected among mertk−/− bone marrow-derived dendritic cell (BMDC) populations. This was observed in both resting BMDC, and BMDC stimulated with lipopolysaccharide (LPS) or treated with exogenous apoptotic cells. We also found that dendritic cells in general have a pro-survival effect on resting B cells in co-culture. However, despite containing more BAFF-secreting cells, mertk−/− BMDC were not superior to C57BL/6 or baff-deficient BMDC at promoting B cell survival. Furthermore, using decoy receptors, we show that dendritic cells may promote B cell survival and autoimmunity through a BAFF-and APRIL-independent mechanism.
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