Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells
- 14 July 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 14 (9), 959-965
- https://doi.org/10.1038/ni.2649
Abstract
Foxp3+ regulatory T (Treg) cells are a crucial immunosuppressive population of CD4+ T cells, yet the homeostatic processes and survival programs that maintain the Treg cell pool are poorly understood. Here we report that peripheral Treg 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 Treg cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-xL and Bcl-2 were dispensable for survival of Treg cells, whereas Mcl-1 was critical for survival of Treg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways.Keywords
This publication has 59 references indexed in Scilit:
- IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasisSeminars in Immunology, 2012
- Defective cell death signalling along the Bcl-2 regulated apoptosis pathway compromises Treg cell development and limits their functionality in miceJournal of Autoimmunity, 2012
- Preferential control of induced regulatory T cell homeostasis via a Bim/Bcl-2 axisCell Death & Disease, 2012
- Deciphering the rules of programmed cell death to improve therapy of cancer and other diseasesThe EMBO Journal, 2011
- Fate Mapping Reveals Separate Origins of T Cells and Myeloid Lineages in the ThymusImmunity, 2010
- Intraclonal competition limits the fate determination of regulatory T cells in the thymusNature Immunology, 2009
- Differentiation of regulatory Foxp3+T cells in the thymic cortexProceedings of the National Academy of Sciences of the United States of America, 2008
- The BCL-2 protein family: opposing activities that mediate cell deathNature Reviews Molecular Cell Biology, 2008
- Opposing Functions of the T Cell Receptor Kinase ZAP-70 in Immunity and Tolerance Differentially Titrate in Response to Nucleotide SubstitutionsImmunity, 2007
- Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune diseaseProceedings of the National Academy of Sciences of the United States of America, 2005