TGF-β1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune suppression
| Autor: | Yu Zhou, Charles A. Stuart, Baozhen Yao, Haiju Zhang, Clay Wheeler, Yi Caudle, Deling Yin |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine p38 mitogen-activated protein kinases Immunology chemical and pharmacologic phenomena Smad2 Protein Article Immune tolerance Transforming Growth Factor beta1 Mice 03 medical and health sciences Immune system Immune Tolerance Animals Immunology and Allergy Chronic stress Smad3 Protein Mice Inbred BALB C Chemistry TLR9 FOXP3 Forkhead Transcription Factors Cell biology 030104 developmental biology Neurology Neurology (clinical) Signal transduction Stress Psychological Signal Transduction Transforming growth factor |
| Zdroj: | Journal of Neuroimmunology. 314:30-41 |
| ISSN: | 0165-5728 |
| Popis: | Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it has been established that chronic stress exerts a significant suppressive effect on immune function, the mechanisms by which affects immune responses remain elusive. By employing an in vivo murine system, we revealed that TGF-β1/Smad2/3/Foxp3 axis was remarkably activated following chronic stress. Furthermore, TLR9 and p38 MAPK played a critical role in the activation of TGF-β1/Smad2/3/Foxp3 signaling cascade. Moreover, inhibition of TGF-β1/Smad2/3/Foxp3 or p38 significantly attenuated chronic stress-induced lymphocyte apoptosis and apoptosis-related proteins, as well as the differentiation of T regulatory cells in spleen. Interestingly, disequilibrium of pro-inflammatory and anti-inflammatory cytokines balance caused by chronic stress was also rescued by blocking TGF-β1/Smad2/3/Foxp3 axis. These findings yield insight into a novel mechanism by which chronic stress modulates immune functions and identifies new targets for the development of novel anti-immune suppressant medications. |
| Databáze: | OpenAIRE |
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