Journal article
Antiapoptotic McI-1 is critical for the survival and niche-filling capacity of Foxp3 regulatory T cells
W Pierson, B Cauwe, A Policheni, SM Schlenner, D Franckaert, J Berges, S Humblet-Baron, S Schönefeldt, MJ Herold, D Hildeman, A Strasser, P Bouillet, LF Lu, P Matthys, AA Freitas, RJ Luther, CT Weaver, J Dooley, DHD Gray, A Liston
Nature Immunology | Published : 2013
DOI: 10.1038/ni.2649
Abstract
Foxp3+ regulatory T (T reg) cells are a crucial immunosuppressive population of CD4+ T cells, yet the homeostatic processes and survival programs that maintain the T reg cell pool are poorly understood. Here we report that peripheral T reg cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2-dependent and costimulation-dependent process. By contrast, excess T reg cells are removed by attrition, dependent on the Bim-initiated Bak-and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-x L and Bcl-2 were dispensable for survival of T reg cells, whereas Mcl-1 was critical for survival of T reg cells, and..
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Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
We thank P. Fink (University of Washington, Seattle) for providing Rag2-GFP-Tg mice backcrossed to the B6 background, L. Hennighausen (US National Institutes of Health) for providing Bcl2l1<SUP>fx</SUP> mice, A. Rudensky (Memorial Sloan-Kettering Cancer Center) for providing Foxp3<SUP>GFP</SUP>, Foxp3<SUP>Cre</SUP>, Foxp3<SUP>Thy1.1</SUP> and Foxp3<SUP>DTR</SUP> mice, G. Kelly and S. Grabow (Walter and Eliza Hall Institute of Medical Research) for CreERT2Mcl1<SUP>fl</SUP> and CreERT2Bcl2l1<SUP>flox</SUP> mice and Bcl2<SUP>-/-</SUP> fetal liver samples, F. Kupresanin, G. Siciliano, G.-F. Dabrowski, K. Humphreys and E. Lanera (Walter and Eliza Hall Institute of Medical Research) for technical assistance, S. Korsmeyer (Harvard Medical School) for BaxflBak1<SUP>-/-</SUP> mice, and A. Kallies for critical feedback on the manuscript. This work was supported by grants from the VIB, Marie Curie (TREG to A. L.), European Research Council (IMMUNO to A. L.), Interuniversity Attraction Poles (VII/39 to A. L and P. M.), QSIS (to A. A. F.) and the Australian National Health and Medical Research Council (CDF-1 #637353 to D. H. D. G.). W. P. is funded by Agentschap voor Innovatie door Wetenschap en Technologie. B. C., S. M. S. and S.H.-B. are funded by the Fonds Wetenschappelijk Onderzoek. This work was made possible through Victorian State Government Operational Infrastructure Support and the Australian Government National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme.