The Decoy Receptor 3 (DcR3, TNFRSF6B) suppresses Th17 immune responses and is abundant in human cerebrospinal fluid.
The Decoy Receptor 3 (DcR3) is known to compete with the signalling receptors of the Fas ligand (FasL), LIGHT and the TNF-like molecule 1A (TL1A). The primary aim of this study was to provide insights into the role of DcR3 in the modulation of myelin-specific encephalitogenic autoimmune T cell responses. Treatment of PLP-specific lymph node cells with DcR3.Fc protein resulted in a suppression of IFN-g and IL-17, in a reduced proportion of Th17 cells and in a decrease of encephalitogenicity. The Th17 response promoting cytokines IL-6 and IL-23 were suppressed by DcR3.Fc as well. DcR3.Fc-treatment of CD4+ T cells with a defective FasL did not influence the production of IL-17 indicating that DcR3 suppresses IL-17 production by disruption of Fas-FasL interactions. We identified high concentrations of DcR3 in the cerebrospinal fluid (CSF) of patients with various neurological disease states while almost no DcR3 was detected in corresponding serum samples. In conclusion, DcR3 modulates CNS-autoimmunity by interfering with Th17 responses via blockade of Fas-FasL interaction. The anti-inflammatory properties and high DcR3 concentrations in the CSF warrant further investigations in the expression pattern and the function of DcR3 within the CNS.
Mueller
André M
AM
Department of Neurology, University of Regensburg, Regensburg, Germany. amueller@msrcny.org
Pedré
Xiomara
X
Killian
Stephan
S
David
Monique
M
Steinbrecher
Andreas
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000503:physiopathology; D053222:Fas Ligand Protein / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000134:cerebrospinal fluid* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism
D053222:Fas Ligand Protein; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D007371:Interferon-gamma