Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress

Abstract

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol-or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1␣/CXCL12. Cortisol doseand time-dependently augmented CXCR4 expression on T lymphocytes, with Ͻ6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise. chemokine receptor; glucocorticoid; T cell distribution

Cortisol and epinephrine control opposing circadian rhythms in T cell subsets

“…35 Glucocorticoids enhance CXCR4 expression and signaling in T cells in vitro. 37,38 Here we extend this observation by showing increased CXCR4 expression in the different T cell subsets of interest after incubation with low, physiologic concentrations of cortisol. This analysis, together with comparisons of blood sampled in the morning vs evening, points to a most pronounced cortisolinduced up-regulation of CXCR4 in naive and central memory CD4 ϩ and CD8 ϩ T cell subsets.…”

Glucocorticoids Suppress CCR9-Mediated Chemotaxis, Calcium Flux, and Adhesion to MAdCAM-1 in Human T Cells

“…2C). These results are in accord with reports that DEX increases CXCR4 surface expression and CXCL12-mediated chemotaxis through activation of the GC receptor (22,23).…”

“…As a control, we compared the effects of GCs on CXCR4, which is coexpressed on CCR9 + T cells. CXCR4 is stimulated by a single ligand, CXCL12, and consistent with previous reports, GCs increase CXCR4 expression and enhance CXCL12-mediated functions (22,23). These results identify novel effects of GCs on the function of primary human T cells that are likely to be physiologically and clinically relevant in intestinal inflammation.…”

“…Interestingly, following corticosteroid treatment, the direction and magnitude of effects were not universally shared among three studied chemokine receptors: CXCR3 surface expression was reduced whereas CCR9 was unaffected; both CCR9-and CXCR3-mediated chemotaxis were suppressed; and coexpressed CXCR4 had increased surface expression and enhanced downstream functions. The observations relating to CCR9 and CXCR3 are novel, whereas the effect of DEX on CXCR4 has been previously described (22,23).…”

Histological and Immunohistochemical Study on the Effect of Constant Light Exposure on T Lymphocyte Subsets in the Thymus and Lymph Node of Male Albino Rats

“…CXCR4 mediates the homing of T cells to lymph nodes [48] . Glucocorticoids affect T cells which had lymph node-homing capacity and redirect them from the blood to the bone marrow [49] . The appearance of many CD3 positive cells in the lymphoid follicles could be explained by the finding of Hoshi et al, 2002 [50] who found dividing T cells engaged in the cell cycle moved towards the germinal center from T dependant zone.…”