'Ghost Lab', T Cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Nat Med. 2011 Nov 20;17(12):1585-93. doi: 10.1038/nm.2505.
Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell-deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans.
采用系统生物学方法，我们发现并剖析了免疫系统、肠道上皮和微生物群之间的三向相互作用。我们发现，在没有 B 细胞或 IgA 的情况下，并且存在微生物群的情况下，肠道上皮会启动自身的保护机制，上调干扰素诱导的免疫反应途径，同时抑制 Gata4 相关的代谢功能。这种肠道功能的转变导致脂质吸收不良和体脂肪沉积减少。网络分析显示，存在两个相互关联的上皮细胞基因网络，一个控制脂质代谢，另一个调节免疫，它们的表达相反。来自患有普通可变免疫缺陷或 HIV 感染和肠道吸收不良的个体的肠道活检的基因表达模式与 B 细胞缺陷小鼠非常相似，这为人类免疫缺陷和脂质吸收不良之间长期存在的神秘关联提供了一种可能的解释。
