T-cell development and function are modulated by dual specificity phosphatase DUSP5
Graduate School of Biomedical Sciences; Laboratory of Molecular Immunology
Life Sciences | Medicine and Health Sciences
Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates lymphocyte proliferation and peripheral tolerance. IL-2 activates mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and signal transducer and activator of transcription (STAT) pathways and modulates expression of target genes. Systematic analysis of IL-2 target genes has revealed regulation of potential feedback inhibitors of IL-2 signaling, including several suppressor of cytokine signaling (SOCS) family members as well as MAPK pathway-regulating dual specificity phosphatases (DUSPs). Here we have evaluated the in vivo actions of DUSP5, an extracellular signal-regulated kinase 1/2 (ERK1/2)-specific phosphatase, by generating transgenic mice overexpressing DUSP5 within the lymphoid compartment. We show that transgenic DUSP5 expression results in a block in thymocyte development at the double positive stage. We also demonstrate that DUSP5-expressing mature T cells exhibit decreased IL-2-dependent proliferation and defective IL-2-mediated induction of genes. Finally, DUSP5 transgenic mice develop autoimmune symptoms, suggesting a role for the MAPK pathway in the regulation of tolerance. Thus, proper regulation of DUSP5 activity is critical for normal immune system development, IL-2 actions, and tolerance.
DOI of Published Version
J Biol Chem. 2008 Jun 20;283(25):17362-9. Epub 2008 Apr 21. Link to article on publisher's site
The Journal of biological chemistry
Kovanen PE, Bernard J, Al-Shami A, Liu C, Bollenbacher-Reilley J, Young L, Pise-Masison CA, Spolski R, Leonard WJ. (2008). T-cell development and function are modulated by dual specificity phosphatase DUSP5. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1074/jbc.M709887200. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1489