NDLI: Histone Deacetylase 3 Is Required for T Cell Maturation.

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Histone Deacetylase 3 Is Required for T Cell Maturation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hsu, Fan-Chi Shapiro, Virginia Smith Chen, Meibo W. McWilliams, Douglas C. Belmonte, Paul J. Constans, Megan M. Hiebert, Scott W.
Description	Author Affiliation: Hsu FC ( Department of Immunology, Mayo Clinic, Rochester, MN 55905); Belmonte PJ ( Department of Immunology, Mayo Clinic, Rochester, MN 55905); Constans MM ( Department of Immunology, Mayo Clinic, Rochester, MN 55905); Chen MW ( Department of Immunology, Mayo Clinic, Rochester, MN 55905); McWilliams DC ( Department of Immunology, Mayo Clinic, Rochester, MN 55905); Hiebert SW ( Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.); Shapiro VS ( Department of Immunology, Mayo Clinic, Rochester, MN 55905)
Abstract	Recent thymic emigrants are newly generated T cells that need to undergo postthymic maturation to gain functional competency and enter the long-lived naive T cell pool. The mechanism of T cell maturation remains incompletely understood. Previously, we demonstrated that the transcriptional repressor NKAP is required for T cell maturation. Because NKAP associates with histone deacetylase 3 (HDAC3), we examined whether HDAC3 is also required for T cell maturation. Although thymic populations are similar in CD4-cre HDAC3 conditional knockout mice compared with wild-type mice, the peripheral numbers of CD4(+) and CD8(+) T cells are dramatically decreased. In the periphery, the majority of HDAC3-deficient naive T cells are recent thymic emigrants, indicating a block in T cell maturation. CD55 upregulation during T cell maturation is substantially decreased in HDAC3-deficient T cells. Consistent with a block in functional maturation, HDAC3-deficient peripheral T cells have a defect in TNF licensing after TCR/CD28 stimulation. CD4-cre HDAC3 conditional knockout mice do not have a defect in intrathymic migration, thymic egress, T cell survival, or homeostasis. In the periphery, similar to immature NKAP-deficient peripheral T cells, HDAC3-deficient peripheral T cells were bound by IgM and complement proteins, leading to the elimination of these cells. In addition, HDAC3-deficient T cells display decreases in the sialic acid modifications on the cell surface that recruit natural IgM to initiate the classical complement pathway. Therefore, HDAC3 is required for T cell maturation.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1500435
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Histone Deacetylases Metabolism T-lymphocytes Cytology Animals Bone Marrow Cells Genetics Immunology Cell Movement Complement Activation Complement System Proteins Homeostasis Interleukin-7 Lymphocyte Count Mice Mice, Knockout Mice, Transgenic T-lymphocyte Subsets Thymus Gland Tumor Necrosis Factors Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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