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Dual Specificity Phosphatase 5 Is Essential for T Cell Survival. PLoS One 2016;11(12):e0167246

Date

12/10/2016

Pubmed ID

27936095

Pubmed Central ID

PMC5147890

DOI

10.1371/journal.pone.0167246

Scopus ID

2-s2.0-85006064690   11 Citations

Abstract

The mitogen-activated protein kinase (MAPK) pathway regulates many key cellular processes such as differentiation, apoptosis, and survival. The final proteins in this pathway, ERK1/2, are regulated by dual specificity phosphatase 5 (DUSP5). DUSP5 is a nuclear, inducible phosphatase with high affinity and fidelity for ERK1/2. By regulating the final step in the MAPK signaling cascade, DUSP5 exerts strong regulatory control over a central cellular pathway. Like other DUSPs, DUSP5 plays an important role in immune function. In this study, we have utilized new knockout mouse reagents to explore its function further. We demonstrate that global loss of DUSP5 does not result in any gross phenotypic changes. However, loss of DUSP5 affects memory/effector CD8+ T cell populations in response to acute viral infection. Specifically, Dusp5-/- mice have decreased proportions of short-lived effector cells (SLECs) and increased proportions of memory precursor effector cells (MPECs) in response to infection. Further, we show that this phenotype is T cell intrinsic; a bone marrow chimera model restricting loss of DUSP5 to the CD8+ T cell compartment displays a similar phenotype. Dusp5-/- T cells also display increased proliferation, increased apoptosis, and altered metabolic profiles, suggesting that DUSP5 is a pro-survival protein in T cells.

Author List

Kutty RG, Xin G, Schauder DM, Cossette SM, Bordas M, Cui W, Ramchandran R

Authors

Weiguo Cui PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Blotting, Western
CD8-Positive T-Lymphocytes
Cell Proliferation
Cell Survival
Cells, Cultured
Dual-Specificity Phosphatases
Gene Expression Regulation, Enzymologic
Interferon-gamma
Lymphocytic choriomeningitis virus
Mice, Inbred C57BL
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d