IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4 + Foxp3 + regulatory T lymphocytes.

Autor:	Apert C; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., Galindo-Albarrán AO; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France.; Station d'Ecologie Théorique et Expérimentale, CNRS, Moulis, France., Castan S; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., Detraves C; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., Michaud H; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., McJannett N; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., Haegeman B; Station d'Ecologie Théorique et Expérimentale, CNRS, Moulis, France., Fillatreau S; Institut Necker Enfants Malades, Inserm U1151, CNRS UMR8253, Paris, France.; Université de Paris Descartes, Faculté de Médecine, Paris, France.; AP-HP, Hôpital Necker-Enfants Malades, Paris, France., Malissen B; Centre d'Immunophénomique (CIPHE), Aix Marseille Université, INSERM, CNRS, Marseille, France., Holländer G; Paediatric Immunology, Department of Biomedicine, University of Basel and University Children's Hospital Basel, Basel, Switzerland.; Department of Paediatrics and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Žuklys S; Paediatric Immunology, Department of Biomedicine, University of Basel and University Children's Hospital Basel, Basel, Switzerland., Santamaria JC; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., Joffre OP; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., Romagnoli P; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France., van Meerwijk JPM; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 - CNRS UMR5051 - University Toulouse III, Toulouse, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 08; Vol. 13, pp. 965303. Date of Electronic Publication: 2022 Sep 08 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.965303
Abstrakt:	Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. At the age of three weeks, when in wt and IL-15-deficient (but not in IL-2-deficient) mice substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 but not IL-15 modulated the CD25, GITR, OX40, and CD73-phenotypes of the thymus-egress-competent and periphery-seeding Treg-population. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3 sf mice, newly developed Treg from IL-2- (and to a much lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Apert, Galindo-Albarrán, Castan, Detraves, Michaud, McJannett, Haegeman, Fillatreau, Malissen, Holländer, Žuklys, Santamaria, Joffre, Romagnoli and van Meerwijk.)
Databáze:	MEDLINE
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