Journal Article

DKFZ-2026-01271

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png HDAC7 controls anti-viral and anti-tumor immunity by CD8+ T cells.

Yerinde, C. ; Keye, J. ; Hsiao, H.-J. ; Durlanik, S. ; Freise, I. ; Nowak, F. ; Letizia, M. ; Schlickeiser, S. ; Obermayer, B. ; Huck, A. ; Friedrich, M. ; Wu, H. ; Kunkel, D. ; Kühl, A. A. ; Bauer, S. ; Thiel, A. ; Hegazy, A. N. ; Siegmund, B.DKFZ* ; Glauben, R.DKFZ* ; Weidinger, C.

2026
Frontiers Media Lausanne

Abstract: Class II histone deacetylases (HDAC) orchestrate T cell-dependent immune responses via the epigenetic control of genes and via the post-translational modification of cytoplasmic and nuclear proteins. However, the contribution of single HDAC family members to the differentiation and function of peripheral CD8+ T cells remains elusive. We here demonstrate that HDAC7-deficiency leads to the upregulation of immune checkpoint molecules, increased apoptosis and disturbed glutamine homeostasis of peripheral murine CD8+ T cells, which we could link to a MEF2D-dependent induction of FasL expression ultimately deterring the survival of HDAC7-deficient CD8+ T cells. Likewise, we observed in mouse models of lymphoma, that mice with a T cell-specific deletion of Hdac7 harbor impaired anti-tumor immune responses in syngeneic transfer models of lymphoma and we found that HDAC7 is required for CD8+ T cell-dependent memory recall responses in models of lymphocytic choriomeningitis virus infection. Taken together, we identify HDAC7 as a central regulator of cellular exhaustion and apoptosis of peripheral CD8+ T cells, controlling CD8+ T cell dependent anti-tumor and anti-viral immunity in mice.

Keyword(s): Animals (MeSH) ; Histone Deacetylases: genetics (MeSH) ; Histone Deacetylases: immunology (MeSH) ; Histone Deacetylases: metabolism (MeSH) ; CD8-Positive T-Lymphocytes: immunology (MeSH) ; CD8-Positive T-Lymphocytes: metabolism (MeSH) ; Mice (MeSH) ; Apoptosis (MeSH) ; Mice, Knockout (MeSH) ; Lymphocytic Choriomeningitis: immunology (MeSH) ; Lymphocytic choriomeningitis virus: immunology (MeSH) ; Lymphoma: immunology (MeSH) ; T-Cell Exhaustion (MeSH) ; Mice, Inbred C57BL (MeSH) ; Fas Ligand Protein: metabolism (MeSH) ; Immunologic Memory (MeSH) ; CD8+ T cells ; Eomes ; FasL ; HDAC7 ; apoptosis ; cellular exhaustion ; colitis ; glutamine ; Histone Deacetylases ; Hdac7 protein, mouse ; Fas Ligand Protein

Note: #DKTKZFB26#

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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