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Besedovsky, L.* ; Linz, B.* ; Dimitrov, S.* ; Groch, S.* ; Born, J. ; Lange, T.*

Cortisol increases CXCR4 expression but does not affect CD62L and CCR7 levels on specific T cell subsets in humans.

Am. J. Physiol. Endocrinol. Metab. 306, E1322-E1329 (2014)
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Glucocorticoids are well known to affect T cell migration, leading to a redistribution of the cells from blood to the bone marrow, accompanied by a concurrent suppression of lymph node homing. Despite numerous studies in this context, with most of them employing synthetic glucocorticoids in nonphysiological doses, the mechanisms of this redistribution are not well understood. Here, we investigated in healthy men the impact of cortisol at physiological concentrations on the expression of different migration molecules on eight T cell subpopulations in vivo and in vitro. Hydrocortisone (cortisol, 22 mg) infused during nocturnal rest when endogenous cortisol levels are low, compared with placebo, differentially reduced numbers of T cell subsets, with naive CD4(+) and CD8(+) subsets exhibiting the strongest reduction. Hydrocortisone in vivo and in vitro increased CXCR4 expression, which presumably mediates the recruitment of T cells to the bone marrow. Expression of the lymph node homing receptor CD62L on total CD3(+) and CD8(+) T cells appeared reduced following hydrocortisone infusion. However, this was due to a selective extravasation of CD62L(+) T cell subsets, as hydrocortisone affected neither CD62L expression on a subpopulation level nor CD62L expression in vitro. Corresponding results in the opposite direction were observed after blocking of endogenous cortisol synthesis by metyrapone. CCR7, another lymph node homing receptor, was also unaffected by hydrocortisone in vitro. Thus, cortisol seems to redirect T cells to the bone marrow by upregulating their CXCR4 expression, whereas its inhibiting effect on T cell homing to lymph nodes is apparently regulated independently of the expression of classical homing receptors.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hydrocortisone ; T Cell Migration ; L-selectin ; Ccr7 ; Cxcr4; Thymus-derived Lymphocytes; Stress-induced Changes; Peripheral-blood; Bone-marrow; In-vivo; Glucocorticoid-receptors; Leukocyte Distribution; Corticosteroid Action; Vascular Endothelium; Adhesion Molecules
ISSN (print) / ISBN 0193-1849
e-ISSN 1522-1555
Quellenangaben Volume: 306, Issue: 11, Pages: E1322-E1329 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place Bethesda
Reviewing status Peer reviewed