Dépôt numérique

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

D'Elia, Michele; Patenaude, Julie; Dupras, Charles et Bernier, Jacques (2010). T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids American Journal of Physiology - Endocrinology and Metabolism , vol. 299 , nº 2. E299-307. DOI: 10.1152/ajpendo.00084.2010.

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Glucocorticoids (GC) are steroid hormones that modulate T cell functions and restrain their hyperresponsiveness following stimulation. Naive T lymphocytes are sensitive to GC but become more resistant when they are activated. A balance between activation and inhibition signals is important for a targeted and effective T cell response. Thermal injury is characterized by an immune dysfunction and hyperactive T cells visible at day 10 postburn. In this study, our objective was to evaluate T cell sensitivity to GC following thermal injury and to identify mechanisms that could modulate their sensitivity. One mechanism that we hypothesized was increased p38 mitogen-activated protein kinase (MAPK) activity that could lead to GC resistance. Male C57BL/6 mice underwent a full-thickness 20% total body surface area. At 10 days postinjury, splenic T cells were isolated. Glucocorticoid receptor (GR) expression was higher in T cells from burn-injured mice. Interestingly, these cells were also less sensitive to GC-induced apoptosis prior to and poststimulation. Furthermore, anti-CD3-activated T cells from burn-injured mice showed increased proliferation and CD25 expression, which resisted corticosterone's (CORT) suppressive effect. Anti-CD3-activated CD4(+)CD44(+) memory cells from burn-injured mice expressed the highest level of CD25 and were resistant to CORT. Increased phosphorylation of p38 MAPK was also noted in activated T cells from burn-injured mice. Pharmacological inhibition of p38 MAPK decreased cell proliferation and normalized interferon-gamma (IFNgamma) production. In conclusion, we demonstrate that a unique event like burn injury induces a loss of sensitivity to GC in splenic T cells and have identified p38 MAPK as a key modulator for this resistance.

Type de document: Article
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 29 juin 2024 21:42
Dernière modification: 29 juin 2024 21:42
URI: https://espace.inrs.ca/id/eprint/14572

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