Publication Date:
2014-02-11
Description:
The transcription factors c-Myc and N-Myc--encoded by Myc and Mycn, respectively--regulate cellular growth and are required for embryonic development. A third paralogue, Mycl1, is dispensable for normal embryonic development but its biological function has remained unclear. To examine the in vivo function of Mycl1 in mice, we generated an inactivating Mycl1(gfp) allele that also reports Mycl1 expression. We find that Mycl1 is selectively expressed in dendritic cells (DCs) of the immune system and controlled by IRF8, and that during DC development, Mycl1 expression is initiated in the common DC progenitor concurrent with reduction in c-Myc expression. Mature DCs lack expression of c-Myc and N-Myc but maintain L-Myc expression even in the presence of inflammatory signals such as granulocyte-macrophage colony-stimulating factor. All DC subsets develop in Mycl1-deficient mice, but some subsets such as migratory CD103(+) conventional DCs in the lung and liver are greatly reduced at steady state. Importantly, loss of L-Myc by DCs causes a significant decrease in in vivo T-cell priming during infection by Listeria monocytogenes and vesicular stomatitis virus. The replacement of c-Myc by L-Myc in immature DCs may provide for Myc transcriptional activity in the setting of inflammation that is required for optimal T-cell priming.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954917/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉KC, Wumesh -- Satpathy, Ansuman T -- Rapaport, Aaron S -- Briseno, Carlos G -- Wu, Xiaodi -- Albring, Jorn C -- Russler-Germain, Emilie V -- Kretzer, Nicole M -- Durai, Vivek -- Persaud, Stephen P -- Edelson, Brian T -- Loschko, Jakob -- Cella, Marina -- Allen, Paul M -- Nussenzweig, Michel C -- Colonna, Marco -- Sleckman, Barry P -- Murphy, Theresa L -- Murphy, Kenneth M -- P30 CA091842/CA/NCI NIH HHS/ -- P30 CA91842/CA/NCI NIH HHS/ -- R01 AI024157/AI/NIAID NIH HHS/ -- R01 AI047829/AI/NIAID NIH HHS/ -- T32 AI007163/AI/NIAID NIH HHS/ -- T32 GM007200/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 13;507(7491):243-7. doi: 10.1038/nature12967. Epub 2014 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA. ; Department of Medicine A, Hematology and Oncology, University of Muenster, 48149 Muenster, Germany. ; Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA. ; 1] Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA [2] Howard Hughes Medical Institute, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24509714" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD/metabolism
;
Cell Division
;
Cross-Priming/*immunology
;
Dendritic Cells/cytology/*immunology/*metabolism
;
Female
;
*Gene Expression Regulation
;
Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
;
Inflammation/immunology/metabolism
;
Integrin alpha Chains/metabolism
;
Interferon Regulatory Factors/metabolism
;
Listeria monocytogenes/immunology
;
Liver/cytology/immunology
;
Lung/cytology/immunology
;
Male
;
Mice
;
Proto-Oncogene Proteins c-myc/deficiency/*metabolism
;
T-Lymphocytes/*immunology
;
Transcription, Genetic
;
Vesiculovirus/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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