IFN-α promotes rapid human Treg contraction and late Th1-like Treg decrease
| Autor: | Vincenzo Barnaba, Silvia Piconese, Daniele Accapezzato, Eliana M. Coccia, Giancarlo Labbadia, Gabriella d'Ettorre, Eugenio Nelson Cavallari, Fabiana Rizzo, Vincenzo Vullo, Eleonora Timperi, Martina Severa, Ilenia Pacella, Carmela Martire, Ludovica Calvo |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Myeloid Adolescent Regulatory T cell Immunology Inflammation Hepacivirus Biology Lymphocyte Activation Antiviral Agents T-Lymphocytes Regulatory IL-1 STAT apoptosis desensitization stat 03 medical and health sciences 0302 clinical medicine T-Lymphocyte Subsets In vivo Immunity medicine Humans Immunology and Allergy Aged Interferon-alpha Dendritic Cells Cell Biology Hepatitis C Chronic Middle Aged Th1 Cells 030104 developmental biology medicine.anatomical_structure Apoptosis Interleukin 12 Cancer research Cytokines Female medicine.symptom 030215 immunology |
| Popis: | Type I IFNs are pleiotropic cytokines that exert concerted activities in the development of antiviral responses. Regulatory T cells represent a physiologic checkpoint in the balance between immunity and tolerance, requiring fine and rapid controls. Here, we show that human regulatory T cells are particularly sensitive to the sequential effects of IFN-α. First, IFN-α exerts a rapid, antiproliferative and proapoptotic effect in vitro and in vivo, as early as after 2 d of pegylated IFN/ribavirin therapy in patients with chronic hepatitis C. Such activities result in the decline, at d 2, in circulating regulatory T cell frequency and specifically of the activated regulatory T cell subset. Later, IFN-based therapy restrains the fraction of regulatory T cells that can be polarized into IFN-γ-producing Th1-like regulatory T cells known to contribute to chronic immune activation in type 1 inflammation. Indeed, Th1-like regulatory T cell frequency significantly declines after 30 d of therapy in vivo in relation to the persistent decline of relevant IL-12 sources, namely, myeloid and 6-sulfo LacNAc-expressing dendritic cells. This event is recapitulated by experiments in vitro, providing evidence that it may be attributable to the inhibitory effect of IFN-α on IL-12-induced, Th1-like regulatory T cell polarization. In summary, our results suggest that IFN-α-driven, early regulatory T cell depletion contributes to the development of antiviral immunity, ultimately resulting in the resolution of type 1 inflammation. |
| Databáze: | OpenAIRE |
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