Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/18438
Título: Human regulatory T-cell development is dictated by Interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus
Autor: Caramalho, I.
Nunes-Silva, V.
Pires, A. R.
Mota, C.
Pinto, A. I.
Nunes-Cabaço, H.
Foxall, R. B.
Sousa, A. E.
Palavras-chave: Common gamma-chain cytokines
Regulatory T cells
Immune tolerance
Human T-cell development
Data: 2014
Editora: Elsevier
Citação: Journal of Autoimmunity 56 (2015) 98e110
Resumo: Thymus-derived FOXP3-expressing regulatory T-cells (tTregs) are master orchestrators of physiological and pathological immune responses, thus constituting ideal targets for the treatment of autoimmunity. Despite their clinical importance, the developmental program governing their differentiation in the human thymus remains poorly understood. Here, we investigated the role of common gamma-chain cytokines in human tTreg differentiation, by performing gain- and loss-of-function experiments in 3D and 2D postnatal thymic cultures. We identified IL-2 and IL-15 as key molecular determinants in this process and excluded a major function for IL-4, IL-7 and IL-21. Mechanistically, IL-2 and IL-15 were equally able to drive tTreg precursor differentiation into FOXP3(+) cells, and promote tTreg proliferation and survival. Both cytokines also increased the expression levels of molecules associated with effector function within FOXP3(+) subsets, supporting their involvement in tTreg functional maturation. Furthermore, we revealed that IL-2 and IL-15 are expressed in a non-overlapping pattern in the human thymus, with the former produced mainly by mature αβ and γδ thymocytes and the latter by monocyte/macrophages and B lymphocytes. Our results identify core mechanisms dictating human tTreg development, with IL-2 and IL-15 defining specific niches required for tTreg lineage stabilization and differentiation, with implications for their therapeutic targeting in autoimmune conditions.
Descrição: © 2014 Elsevier Ltd. All rights reserved.
Peer review: yes
URI: http://dx.doi.org/10.1016/j.jaut.2014.11.002
ISSN: 0896-8411
Versão do Editor: The definitive version is available at http://www.sciencedirect.com
Aparece nas colecções:IMM - Artigos em Revistas Internacionais
FM-LIC - Artigos em Revistas Internacionais

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