DUSP4

Dual specificity protein phosphatase 4 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity protein phosphatase hVH2) (Mitogen-activated protein kinase phosphatase 2) (MAP kinase phosphatase 2) (MKP-2) [MKP2] [VH2]

Publications

Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age.

PubMed

Full text

T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.

MeSH Terms

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aging
• Animals
• B-Lymphocytes
• Biomarkers
• CD4-Positive T-Lymphocytes
• Dual-Specificity Phosphatases
• Gene Silencing
• Humans
• Immunity, Humoral
• Immunologic Memory
• Influenza, Human
• Lymphocyte Activation
• Mice
• Mitogen-Activated Protein Kinase Phosphatases
• Protein Tyrosine Phosphatases
• Signal Transduction
• T-Lymphocytes, Helper-Inducer
• Vaccination
• Young Adult