| Autor: |
Gaëlle Tilly, Tra-My Doan-Ngoc, Michelle Yap, Aurélie Caristan, Lola Jacquemont, Richard Danger, Marion Cadoux, Sarah Bruneau, Magali Giral, Pierrick Guerif, Bryan Nicol, Alexandra Garcia, David-Axel Laplaud, Sophie Brouard, Claire Pecqueur Hellman, Nicolas Degauque |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 8 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2017.00778 |
| Popis: |
The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM). IL-15 induces antiapoptotic signals and promotes proliferation dependent of PI3K/Akt, MAPK, and ERK pathways. Without ex vivo stimulation, TEMRA cells are metabolically more active than naive and EM, as shown by their high ATP reservoir and a high expression of genes involved in glycolysis, glutaminolysis, and the Pentose Phosphate Pathway. Upon stimulation, TEMRA adapt their metabolism by sustaining an increased mitochondrial respiration and glycolysis. Finally, we show that the inhibition of glycolysis is highly effective in preventing endothelial inflammation induced by TEMRA from KT recipients. Together, our findings highlight the metabolic fitness that tightly regulates the immune function of TEMRA in physiological and pathogenic situations. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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