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

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

Research output: Contribution to journalArticlepeer-review

Abstract

NKAP and HDAC3 are critical for T cell maturation. NKAP and HDAC3 physically associate, and a point mutation in NKAP, NKAP(Y352A), abrogates this interaction. To evaluate the significance of NKAP and HDAC3 association in T cell maturation, transgenic mice were engineered for cre-mediated endogenous NKAP gene deletion coupled to induction of NKAP(Y352A) or a wild type (WT) control transgene, NKAP(WT), in double positive thymocytes or regulatory T cells (Tregs). T cell maturation was normal in mice with endogenous NKAP deletion coupled to NKAP(WT) induction. However, severe defects occurred in T cell and Treg maturation and in iNKT cell development when NKAP(Y352A) was induced, recapitulating NKAP deficiency. Conventional T cells expressing NKAP(Y352A) failed to enter the long-term T cell pool, did not produce cytokines, and remained complement susceptible, whereas Tregs expressing NKAP(Y352A) were eliminated as recent thymic emigrants leading to lethal autoimmunity. Overall, these results demonstrate the significance of NKAP–HDAC3 association in T cells.

Original languageEnglish (US)
Pages (from-to)352-367
Number of pages16
JournalImmunoHorizons
Volume3
Issue number8
DOIs
StatePublished - Aug 1 2019

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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