TY - JOUR
T1 - The Interaction between NKAP and HDAC3 Is Critical for T Cell Maturation
AU - Dash, Barsha
AU - Shapiro, Michael J.
AU - Thapa, Puspa
AU - Arocha, Sinibaldo Romero
AU - Chung, Ji Young
AU - Schwab, Aaron D.
AU - McCue, Shaylene A.
AU - Rajcula, Matthew J.
AU - Shapiro, Virginia Smith
N1 - Publisher Copyright:
Copyright © 2019 The Authors.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
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U2 - 10.4049/immunohorizons.1900052
DO - 10.4049/immunohorizons.1900052
M3 - Article
C2 - 31387873
AN - SCOPUS:85106330642
SN - 2573-7732
VL - 3
SP - 352
EP - 367
JO - ImmunoHorizons
JF - ImmunoHorizons
IS - 8
ER -