title: TNFR1 is essential for CD40, but not for lipopolysaccharide-induced sickness behavior and clock gene dysregulation.
abstract: 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.
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Y44-J7 Winterthurerstr. 190, CH-8057 Zurich, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Taraborrelli
authors.forename: Svitlana
authors.initials: S
authors.lastname: Palchykova
authors.forename: Irene
authors.initials: I
authors.lastname: Tobler
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Gast
authors.forename: Thomas
authors.initials: T
authors.lastname: Birchler
authors.forename: Adriano
authors.initials: A
authors.lastname: Fontana
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D056926:CLOCK Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D055809:Illness Behavior / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000235:genetics / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I; D056926:CLOCK Proteins