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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhong, Xiao-Ping Gorentla, Balachandra K. Inoue, Makoto Grayson, Jason M. Fukunaga, Rikiro Shinohara, Mari L. Krishna, Sruti Shin, Jinwook |
| Description | Country affiliation: United States Author Affiliation: Gorentla BK ( Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.) |
| Abstract | T cell development and activation are usually accompanied by expansion and production of numerous proteins that require active translation. The eukaryotic translation initiation factor 4E (eIF4E) binds to the 5' cap structure of mRNA and is critical for cap-dependent translational initiation. It has been hypothesized that MAPK-interacting kinase 1 and 2 (Mnk1/2) promote cap-dependent translation by phosphorylating eIF4E at serine 209 (S209). Pharmacologic studies using inhibitors have suggested that Mnk1/2 have important roles in T cells. However, genetic evidence supporting such conclusions is lacking. Moreover, the signaling pathways that regulate Mnk1/2 in T cells remain unclear. We demonstrate that TCR engagement activates Mnk1/2 in primary T cells. Such activation is dependent on Ras-Erk1/2 signaling and is inhibited by diacylglycerol kinases and ζ. Mnk1/2 double deficiency in mice abolishes TCR-induced eIF4E S209 phosphorylation, indicating their absolute requirement for eIF4E S209 phosphorylation. However, Mnk1/2 double deficiency does not affect the development of conventional ß T cells, regulatory T cells, or NKT cells. Furthermore, T cell activation, in vivo primary and memory CD8 T cell responses to microbial infection, and NKT cell cytokine production were not obviously altered by Mnk1/2 deficiency. Although Mnk1/2 deficiency causes decreased IL-17 and IFN-γ production by CD4 T cells following immunization of mice with myelin oligodendrocyte glycoprotein peptide in complete Freund's adjuvant, correlating with milder experimental autoimmune encephalomyelitis scores, it does not affect Th cell differentiation in vitro. Together, these data suggest that Mnk1/2 has a minimal role in T cell development and activation but may regulate non-T cell lineages to control Th1 and Th17 differentiation in vivo. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1200026 |
| Journal | The Journal of Immunology |
| Issue Number | 3 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Encephalomyelitis, Autoimmune, Experimental Enzymology Lymphocyte Activation Physiology Lymphopoiesis Protein-serine-threonine Kinases T-lymphocyte Subsets Immunology Adoptive Transfer Aniline Compounds Pharmacology Animals Cells, Cultured Drug Effects Eukaryotic Initiation Factor-4e Metabolism Interferon-gamma Biosynthesis Genetics Interleukin-17 Listeriosis Lymphocytic Choriomeningitis Map Kinase Signaling System Mice Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Myelin-oligodendrocyte Glycoprotein Natural Killer T-cells Ovalbumin Peptide Fragments Phosphorylation Protein Processing, Post-translational Antagonists & Inhibitors Deficiency Purines Rna Caps Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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