Institute of Experimental Immunology, University of Zurich, Y44-J7 Winterthurerstr. 190, CH-8057 Zurich, Switzerland.
Brain Behav Immun. 2011 Mar;25(3):434-42. doi: 10.1016/j.bbi.2010.11.001. Epub 2010 Nov 11.
Autoimmune and infectious diseases are associated with behavioral changes referred to as sickness behavior syndrome (SBS). In autoimmunity, the generation of anti-self T lymphocytes and autoantibodies critically involves binding of CD40 ligand on T-cells to its receptor CD40 on B-cells, dendritic cells and macrophages. Activation of CD40 leads to production of proinflammatory cytokines and, as shown here, induces SBS. Here we report that these behavioral changes depend on the expression of tumor necrosis factor alpha receptor 1 (TNFR1), but not on interleukin-1 receptor 1 or interleukin-6. Moreover, the intensity of SBS correlates with suppression of E-box controlled clock genes, including Dbp, and upregulation of Bmal1. However, the absence of TNFR1 does not interfere with the development of SBS and dysregulation of clock genes in mice treated with lipopolysaccharide. Thus, our results suggest that TNFR1 mediates SBS and dysregulation of clock genes in autoimmune diseases.
自身免疫和传染病与被称为疾病行为综合征 (SBS) 的行为变化有关。在自身免疫中，抗自身 T 淋巴细胞和自身抗体的产生关键涉及 T 细胞上的 CD40 配体与其在 B 细胞、树突状细胞和巨噬细胞上的受体 CD40 的结合。CD40 的激活导致促炎细胞因子的产生，正如这里所示，诱导 SBS。我们在这里报告这些行为变化取决于肿瘤坏死因子受体 1 (TNFR1) 的表达，但不依赖于白细胞介素 1 受体 1 或白细胞介素 6。此外，SBS 的强度与 E 盒控制的时钟基因（包括 Dbp）的抑制和 Bmal1 的上调相关。然而，TNFR1 的缺失并不干扰用脂多糖处理的小鼠中 SBS 的发展和时钟基因的失调。因此，我们的结果表明 TNFR1 介导自身免疫性疾病中的 SBS 和时钟基因的失调。
