Human CD4+CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop
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- Marco Cosentino
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Anna Maria Fietta
- Department of Hematological, Pneumological, and Cardiovascular Sciences, University of Pavia, Italy
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- Marco Ferrari
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Emanuela Rasini
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Raffaella Bombelli
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Elena Carcano
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Federica Saporiti
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Federica Meloni
- Department of Hematological, Pneumological, and Cardiovascular Sciences, University of Pavia, Italy
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- Franca Marino
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
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- Sergio Lecchini
- Department of Clinical Medicine, Section of Experimental and Clinical Pharmacology,
説明
<jats:title>Abstract</jats:title><jats:p>CD4+CD25+ regulatory T lymphocytes (Tregs) are specialized T cells playing a key role in the control of immune homeostasis. Here, we show that human Tregs constitutively express tyrosine hydroxylase (TH, EC 1.14.16.2), the rate-limiting enzyme in the synthesis of catecholamines, and contain substantial amounts of dopamine, norepinephrine, and epinephrine, which are released upon treatment with reserpine. Catecholamine release results in reduced production of interleukin-10 and transforming growth factor-β by Tregs, and in down-regulation of Treg-dependent inhibition of effector T-lymphocyte (Teff) proliferation, which occurs without affecting the production of tumor necrosis factor-α or interferon-γ. Tregs and Teffs express on the cell membrane both D1-like and D2-like dopaminergic receptors to a similar extent (12%-29% of the cells). Catecholamine-dependent down-regulation of Tregs is, however, selectively reversed by pharmacological blockade of dopaminergic D1-like receptors, which in Tregs only (and not in Teffs) are also expressed at the level of mRNA and are functionally coupled to intracellular production of cAMP. These findings indicate that in human Tregs endogenous catecholamines subserve an autocrine/paracrine loop involving dopaminergic pathways and resulting in down-regulation of Treg function.</jats:p>
収録刊行物
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- Blood
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Blood 109 (2), 632-642, 2006-09-19
American Society of Hematology