Martin, Elisabeth M. and Remke, Annika and Pfeifer, Eva and Polz, Johannes and Pietryga-Krieger, Anne and Steffens-Weber, Dorothea and Freudenberg, Marina A. and Mostboeck, Sven and Maennel, Daniela N. (2014) TNFR2 maintains adequate IL-12 production by dendritic cells in inflammatory responses by regulating endogenous TNF levels. INNATE IMMUNITY, 20 (7). pp. 712-720. ISSN 1753-4259, 1753-4267
Full text not available from this repository. (Request a copy)Abstract
Sepsis-induced immune reactions are reduced in TNF receptor 2 (TNFR2)-deficient mice as previously shown. In order to elucidate the underlying mechanisms, the functional integrity of myeloid cells of TNFR2-deficient mice was analyzed and compared to wild type (WT) mice. The capacity of dendritic cells to produce IL-12 was strongly impaired in TNF-deficient mice, mirroring impaired production of IL-12 by WT dendritic cells in sepsis or after LPS or TNF pre-treatment. In addition, TNFR2-deficient mice were refractory to LPS pre-treatment and also to hyper-sensitization by inactivated Propionibacterium acnes, indicating habituation to inflammatory stimuli by the immune response when TNFR2 is lacking. Constitutive expression of TNF mRNA in kidney, liver, spleen, colon and lung tissue, and the presence of soluble TNFR2 in urine of healthy WT mice supported the conclusion that TNF is continuously present in naive mice and controlled by soluble TNFR2. In TNFR2-deficient mice endogenous TNF levels cannot be balanced and the continuous exposure to enhanced TNF levels impairs dendritic cell function. In conclusion, TNF pre-exposure suppresses secondary inflammatory reactions of myeloid cells; therefore, continuous control of endogenous TNF by soluble TNFR2 seems to be essential for the maintenance of adequate sensitivity to inflammatory stimuli.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; EXPERIMENTAL CEREBRAL MALARIA; POLYMICROBIAL SEPSIS; T-CELLS; FACTOR-RECEPTOR; PROPIONIBACTERIUM-ACNES; TRANSMEMBRANE TNF; IMMUNE-RESPONSE; DIVERGENT ROLES; DEFICIENT MICE; Tolerance; tumor necrosis factor; inflammation; immune suppression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Aug 2019 08:52 |
| Last Modified: | 13 Aug 2019 08:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9464 |
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