Medical Biology - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/238

Filters

2017 - 2019 2
Reset filters

Settings
Statistics
Citations
Author: Belz, Gabrielle × Author: Gray, Daniel × Author: Strasser, Andreas × Start date: 2000 × Type: Journal Article ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    CARD11 is dispensable for homeostatic responses and suppressive activity of peripherally induced FOXP3+ regulatory T cells
    Polichen, A ; Horikawa, K ; Milla, L ; Kofler, J ; Bouillet, P ; Belz, GT ; O'Reilly, LA ; Goodnow, CC ; Strasser, A ; Gray, DHD (WILEY, 2019-09)
    FOXP3+ regulatory T (Treg) cells are essential for immunological tolerance and immune homeostasis. Despite a great deal of interest in modulating their number and function for the treatment of autoimmune disease or cancer, the precise mechanisms that control the homeostasis of Treg cells remain unclear. We report a new ENU-induced mutant mouse, lack of costimulation (loco), with atopic dermatitis and Treg cell deficiency typical of Card11 loss-of-function mutants. Three distinct single nucleotide variants were found in the Card11 introns 2, 10 and 20 that cause the loss of CARD11 expression in these mutant mice. These mutations caused the loss of thymic-derived, Neuropilin-1+ (NRP1+ ) Treg cells in neonatal and adult loco mice; however, residual peripherally induced NRP1- Treg cells remained. These peripherally generated Treg cells could be expanded in vivo by the administration of IL-2:anti-IL-2 complexes, indicating that this key homeostatic signaling axis remained intact in CARD11-deficient Treg cells. Furthermore, these expanded Treg cells could mediate near-normal suppression of activated, conventional CD4+ T cells, suggesting that CARD11 is dispensable for Treg cell function. In addition to shedding light on the requirements for CARD11 in Treg cell homeostasis and function, these data reveal novel noncoding Card11 loss-of-function mutations that impair the expression of this critical immune-regulatory protein.
  • Item
    Thumbnail Image
    Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival
    Viant, C ; Guia, S ; Hennessy, RJ ; Rautela, J ; Pham, K ; Bernat, C ; Goh, W ; Jiao, Y ; Delconte, R ; Roger, M ; Simon, V ; Souza-Fonseca-Guimaraes, F ; Grabow, S ; Belz, GT ; Kile, BT ; Strasser, A ; Gray, D ; Hodgkin, PD ; Beutler, B ; Vivier, E ; Ugolini, S ; Huntington, ND (ROCKEFELLER UNIV PRESS, 2017-02)
    Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells. Consistent with this, cycling NK cells expressed higher MCL1 (myeloid cell leukemia 1) levels in both control and BCL2-null mice. Finally, we showed that deletion of BIM restored survival in BCL2-deficient but not MCL1-deficient NK cells. Overall, these data demonstrate an essential role for the binding of BCL2 to BIM in the survival of noncycling NK cells. They also favor a model in which MCL1 is the dominant survival protein in proliferating NK cells.