title: Dual Specificity Phosphatase 5 Is Essential for T Cell Survival.
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.
authors.affiliation: Developmental Vascular Biology Program, Division of Neonatology, Department of Pediatrics, Department of Obstetrics and Gynecology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Raman G
authors.initials: RG
authors.lastname: Kutty
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 Watertown Plank Road, Milwaukee, Wisconsin, United States of America.
authors.forename: Gang
authors.initials: G
authors.lastname: Xin
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 Watertown Plank Road, Milwaukee, Wisconsin, United States of America.|Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Schauder
authors.affiliation: Developmental Vascular Biology Program, Division of Neonatology, Department of Pediatrics, Department of Obstetrics and Gynecology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Cossette
authors.affiliation: Developmental Vascular Biology Program, Division of Neonatology, Department of Pediatrics, Department of Obstetrics and Gynecology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bordas
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8727 Watertown Plank Road, Milwaukee, Wisconsin, United States of America.|Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cui
authors.affiliation: Developmental Vascular Biology Program, Division of Neonatology, Department of Pediatrics, Department of Obstetrics and Gynecology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Ramani
authors.initials: R
authors.lastname: Ramchandran
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D054637:Dual-Specificity Phosphatases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007371:Interferon-gamma / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D054637:Dual-Specificity Phosphatases; C546197:Dusp5 protein, mouse