Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, UK.
Eur J Immunol. 2010 Jan;40(1):117-23. doi: 10.1002/eji.200939863.
Signal regulatory protein alpha (SIRPalpha) and its cognate ligand CD47 have been documented to have a broad range of cellular functions in development and immunity. Here, we investigated the role of SIRPalpha-CD47 signalling in invariant NKT (iNKT) cell responses. We found that CD47 was required for the optimal production of IFN-gamma from splenic iNKT cells following exposure to the alphaGalCer analogue PBS-57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRPalpha was undetectable in the liver of uninfected mice, the hepatic iNKT-cell response to infection was also impaired in CD47-/- mice. However, we found that SIRPalpha was rapidly induced on Kupffer cells following L. donovani infection, via a mechanism involving G-protein-coupled receptors. Thus, we describe a novel amplification pathway affecting cytokine production by hepatic iNKT cells, which may facilitate the breakdown of hepatic tolerance after infection.
信号调节蛋白α（SIRPα）及其同源配体 CD47 在发育和免疫过程中具有广泛的细胞功能。在这里，我们研究了 SIRPα-CD47 信号在不变自然杀伤 T（iNKT）细胞反应中的作用。我们发现，在暴露于αGalCer 类似物 PBS-57 后和体内感染杜氏利什曼原虫后，CD47 是脾 iNKT 细胞产生 IFN-γ所必需的。令人惊讶的是，尽管未感染小鼠肝脏中检测不到 SIRPα，但 CD47-/- 小鼠肝脏中 iNKT 细胞对感染的反应也受到损害。然而，我们发现，在 L. donovani 感染后，Kupffer 细胞中 SIRPα通过 G 蛋白偶联受体被快速诱导。因此，我们描述了一种影响肝脏 iNKT 细胞细胞因子产生的新型扩增途径，这可能有助于感染后打破肝脏耐受。
