The Interaction between NKAP and HDAC3 Is Critical for T Cell Maturation

Dash, Barsha; Shapiro, Michael J.; Thapa, Puspa; Arocha, Sinibaldo Romero; Chung, J.; Schwab, Aaron; McCue, Shaylene; Rajcula, Matthew; Shapiro, Virginia Smith

doi:10.4049/immunohorizons.1900052

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…HDAC3-deficient peripheral T-cells also had lower production of TNFα upon stimulation through TCR and CD28, and were targeted for elimination by the classical complement pathway due to a decrease in the sialic acid modifications on the cell surface. Similar T-cell maturation defects were detected in CD4-cre NKAP cKO, indicating that NKAP and HDAC3 work together to regulate T-cell maturation [ 66 ]. NKAP is a regulator of gene expression with the C-terminal domain that is associated with HDAC3, and this association is critical for T-cell maturation and iNKT cell development.…”

Section: Hdacs In T-cellsmentioning

confidence: 89%

Role of Histone Deacetylases in T-Cell Development and Function

Pieniawska¹,

Iżykowska²

2022

IJMS

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Histone deacetylases (HDACs) are a group of enzymes called “epigenetic erasers”. They remove the acetyl group from histones changing the condensation state of chromatin, leading to epigenetic modification of gene expression and various downstream effects. Eighteen HDACs have been identified and grouped into four classes. The role of HDACs in T-cells has been extensively studied, and it has been proven that many of them are important players in T-cell development and function. In this review, we present the current state of knowledge on the role of HDACs in the early stages of T-cell development but also in the functioning of mature lymphocytes on the periphery, including activation, cytokine production, and metabolism regulation.

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Section: Hdacs In T-cellsmentioning

confidence: 89%

Role of Histone Deacetylases in T-Cell Development and Function

Pieniawska¹,

Iżykowska²

2022

IJMS

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“…Moreover, histone deacetylases (HDACs), important chromatin modification factors, participating in iNKT cell development have been reported. Although HDAC4 does not influence development and function acquisition of iNKT cells [48], loss of HDAC3 or abrogation of the interaction between NKAP and HDAC3 impairs iNKT cell generation [49,50]. Since CAF-1 is intimately associated with HDACs in histone deposition [29,56], whether CHAF1b works along with HDAC3 in the early iNKT cell development remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Chromatin assembly factor 1B critically controls the early development but not function acquisition of invariant natural killer T cells in mice

Luo

et al. 2021

Eur J Immunol

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CD4+CD8+ double‐positive thymocytes give rise to both conventional TCRαβ+ T cells and invariant natural killer T cells (iNKT cells), but these two kinds of cells display different characteristics. The molecular mechanism underlying iNKT cell lineage development and function acquisition remain to be elucidated. We show that the loss of chromatin assembly factor 1B (CHAF1b) maintains the normal development of conventional TCRαβ+ T cells but severely impairs early development of iNKT cells. This dysregulation is accompanied by the impairment in chromatin activation and gene transcription at Vα14‐Jα18 locus. Notably, ectopic expression of a Vα14‐Jα18 TCR rescues Chaf1b‐deficient iNKT cell developmental defects. Moreover, cytokine secretion and antitumor activity are substantially maintained in Vα14‐Jα18 TCR transgene‐rescued Chaf1b‐deficient iNKT cells. Our study identifies CHAF1b as a critical factor that controls the early development but not function acquisition of iNKT cells via lineage‐ and stage‐specific regulation.

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“…How BCL6 mediates chromatin remodeling requires more investigation, but BCL6 can interact with multiple corepressors that may be relevant to iNKT cells including SMRT/NCOR-HDAC3, EZH2-BCOR-RING3, and the LSD1 histone demethylase (87). Interestingly, HDAC3, similar to BCL6, is required at the inception of iNKT cell development, and although it can be recruited to DNA by the transcriptional repressor NKAP, it is possible that it is also directed by BCL6 (88).…”

Section: Genomic Regulation Of Plzfmentioning

confidence: 99%

Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development

Morgan

Kee

2022

The Journal of Immunology

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Innate-like lymphocytes are a subset of lymphoid cells that function as a first line of defense against microbial infection. These cells are activated by proinflammatory cytokines or broadly expressed receptors and are able to rapidly perform their effector functions owing to a uniquely primed chromatin state that is acquired as a part of their developmental program. These cells function in many organs to protect against disease, but they release cytokines and cytotoxic mediators that can also lead to severe tissue pathologies. Therefore, harnessing the capabilities of these cells for therapeutic interventions will require a deep understanding of how these cells develop and regulate their effector functions. In this review we discuss recent advances in the identification of the transcription factors and the genomic regions that guide the development and function of invariant NKT cells and we highlight related mechanisms in other innate-like lymphocytes.

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The Interaction between NKAP and HDAC3 Is Critical for T Cell Maturation

Cited by 5 publications

References 44 publications

Role of Histone Deacetylases in T-Cell Development and Function

Role of Histone Deacetylases in T-Cell Development and Function

Chromatin assembly factor 1B critically controls the early development but not function acquisition of invariant natural killer T cells in mice

Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development

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