Journal article
T Cell Activation Threshold Regulated by E3 Ubiquitin Ligase Cbl-b Determines Fate of Inducible Regulatory T Cells
The Journal of immunology (1950), Vol.191(2), pp.632-639
07/15/2013
DOI: 10.4049/jimmunol.1202068
PMCID: PMC3702637
PMID: 23749633
Abstract
E3 ubiquitin ligase Cbl-b is critical for establishing the threshold for T cell activation, and is essential for induction of T cell anergy. Recent studies suggest that Cbl-b is involved in the development of inducible CD4
+
CD25
+
regulatory T cells (iTregs). In this study, we report that the optimal induction of Foxp3 by naïve CD4
+
CD25
−
T cells requires suboptimal TCR triggering. In the absence of Cbl-b, the TCR strength for optimal Foxp3 induction is down-regulated in vitro. Using TCR transgenic Rag
−/−
mice in combination with Cbl-b deficiency, we show that in vivo iTreg development is also controlled by Cbl-b via tuning the TCR strength. Furthermore, we show that Akt-2 but not Akt-1 regulates Foxp3 expression downstream of Cbl-b. Therefore, we demonstrate that Cbl-b regulates the fate of iTregs via controlling the threshold for T cell activation.
Details
- Title: Subtitle
- T Cell Activation Threshold Regulated by E3 Ubiquitin Ligase Cbl-b Determines Fate of Inducible Regulatory T Cells
- Creators
- Guilin Qiao - Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USAYixia Zhao - Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USAZhenping Li - Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USAPeter Q Tang - Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USAWallace Y Langdon - School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, AustraliaTianlan Yang - Division of Cardiology, Department of Internal Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. ChinaJian Zhang - Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.191(2), pp.632-639
- DOI
- 10.4049/jimmunol.1202068
- PMID
- 23749633
- PMCID
- PMC3702637
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 AI090901 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 07/15/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047799102771
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