Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits.

Autor:	Whyte CE; Immunology Programme, The Babraham Institute, Cambridge, UK., Singh K; Immunology Programme, The Babraham Institute, Cambridge, UK., Burton OT; Immunology Programme, The Babraham Institute, Cambridge, UK.; VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.; Department of Microbiology, Immunology and Transplantation, KU Leuven-University of Leuven, Leuven, Belgium., Aloulou M; Immunology Programme, The Babraham Institute, Cambridge, UK.; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Centre national de la recherche scientifique U5051, Institut national de la santé et de la recherche médicale U1291, University of Toulouse III, Toulouse, France., Kouser L; Immunology Programme, The Babraham Institute, Cambridge, UK., Veiga RV; Immunology Programme, The Babraham Institute, Cambridge, UK., Dashwood A; Immunology Programme, The Babraham Institute, Cambridge, UK., Okkenhaug H; Imaging Facility, The Babraham Institute, Cambridge, UK., Benadda S; Immunology Programme, The Babraham Institute, Cambridge, UK.; Centre de Recherche Sur L'inflammation, Centre national de la recherche scientifique ERL8252, Institut national de la santé et de la recherche médicale U1149, Université de Paris, Paris, France., Moudra A; Immunology Programme, The Babraham Institute, Cambridge, UK., Bricard O; Immunology Programme, The Babraham Institute, Cambridge, UK., Lienart S; Immunology Programme, The Babraham Institute, Cambridge, UK., Bielefeld P; Immunology Programme, The Babraham Institute, Cambridge, UK., Roca CP; Immunology Programme, The Babraham Institute, Cambridge, UK., Naranjo-Galindo FJ; Immunology Programme, The Babraham Institute, Cambridge, UK., Lombard-Vadnais F; Department of Microbiology and Immunology, McGill University, Montréal, Quebec, Canada.; Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, Quebec, Canada., Junius S; VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.; Department of Microbiology, Immunology and Transplantation, KU Leuven-University of Leuven, Leuven, Belgium., Bending D; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Ono MM; Department of Life Sciences, Imperial College London, London, UK, Hochepied T; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.; VIB Center for Inflammation Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium., Halim TYF; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Schlenner S; Department of Microbiology, Immunology and Transplantation, KU Leuven-University of Leuven, Leuven, Belgium., Lesage S; Centre de Recherche Sur L'inflammation, Centre national de la recherche scientifique ERL8252, Institut national de la santé et de la recherche médicale U1149, Université de Paris, Paris, France.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Quebec, Canada., Dooley J; Immunology Programme, The Babraham Institute, Cambridge, UK.; VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.; Department of Microbiology, Immunology and Transplantation, KU Leuven-University of Leuven, Leuven, Belgium., Liston A; Immunology Programme, The Babraham Institute, Cambridge, UK.; VIB Center for Brain and Disease Research, Vlaams Instituut voor Biotechnologie, Leuven, Belgium.; Department of Microbiology, Immunology and Transplantation, KU Leuven-University of Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Jul 04; Vol. 219 (7). Date of Electronic Publication: 2022 Jun 14.
DOI:	10.1084/jem.20212391
Abstrakt:	Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability. (© 2022 Whyte et al.)
Databáze:	MEDLINE
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