T cells require Foxo1 to populate the peripheral lymphoid organs
Open Access
- 30 October 2009
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 39 (11), 2991-2999
- https://doi.org/10.1002/eji.200939427
Abstract
Forkhead transcription factors play critical roles in leukocyte homeostasis. To study further the immunological functions of Foxo1, we generated mice that selectively lack Foxo1 in T cells (Foxo1flox/flox Lck.cre+conditional knockout mice (cKO)). Although thymocyte development appeared relatively normal, Foxo1 cKO mice harbored significantly increased percentages of mature single positive T cells in the thymus as compared with WT mice, yet possessed smaller lymph nodes and spleens that contained fewer T cells. Foxo1 cKO T cells were not more prone to apoptosis, but instead were characterized by a CD62Llo CCR7lo CD44hi surface phenotype, a poorly populated lymphoid compartment in the periphery, and were relatively refractory to TCR stimulation, all of which were associated with reduced expression of Sell, Klf2, Ccr7, and S1pr1. Thus, Foxo1 is critical for naïve T cells to populate the peripheral lymphoid organs by coordinating a molecular program that maintains homeostasis and regulates trafficking.Keywords
This publication has 26 references indexed in Scilit:
- The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansionThe Journal of Experimental Medicine, 2009
- Regulation of NF-κB, Th Activation, and Autoinflammation by the Forkhead Transcription Factor Foxo3aImmunity, 2004
- Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1Nature, 2004
- Phosphatidylinositol 3-Kinase Regulates the CD4/CD8 T Cell Differentiation RatioThe Journal of Immunology, 2003
- The Forkhead Transcription Factor FoxO Regulates Transcription of p27Kip1 and Bim in Response to IL-2The Journal of Immunology, 2002
- T Cell MemoryAnnual Review of Immunology, 2002
- AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1Nature, 2000
- Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription FactorCell, 1999
- Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin.The Journal of Experimental Medicine, 1994
- Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient miceImmunity, 1994