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NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNF AIP3/A20

Michael Drennan (UGent) , Srinath Govindarajan (UGent) , Eveline Verheugen (UGent) , Jonathan Coquet (UGent) , Jens Staal (UGent) , Conor Mc Guire (UGent) , Tom Taghon (UGent) , Georges Leclercq (UGent) , Rudi Beyaert (UGent) , Geert van Loo (UGent) , et al.
(2016) JOURNAL OF EXPERIMENTAL MEDICINE. 213(10). p.1973-1981
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Abstract
Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells.
Keywords
T-CELL DEVELOPMENT, ACTIVATION, NF-KAPPA-B, A20, MALT1, PARACASPASE, LYMPHOCYTES, INHIBITOR, IMMUNITY, TNFAIP3

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Citation

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Chicago
Drennan, Michael, Srinath Govindarajan, Eveline Verheugen, Jonathan Coquet, Jens Staal, Conor Mc Guire, Tom Taghon, et al. 2016. “NKT Sublineage Specification and Survival Requires the Ubiquitin-modifying Enzyme TNF AIP3/A20.” Journal of Experimental Medicine 213 (10): 1973–1981.
APA
Drennan, M., Govindarajan, S., Verheugen, E., Coquet, J., Staal, J., Mc Guire, C., Taghon, T., et al. (2016). NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNF AIP3/A20. JOURNAL OF EXPERIMENTAL MEDICINE, 213(10), 1973–1981.
Vancouver
1.
Drennan M, Govindarajan S, Verheugen E, Coquet J, Staal J, Mc Guire C, et al. NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNF AIP3/A20. JOURNAL OF EXPERIMENTAL MEDICINE. 2016;213(10):1973–81.
MLA
Drennan, Michael, Srinath Govindarajan, Eveline Verheugen, et al. “NKT Sublineage Specification and Survival Requires the Ubiquitin-modifying Enzyme TNF AIP3/A20.” JOURNAL OF EXPERIMENTAL MEDICINE 213.10 (2016): 1973–1981. Print.
@article{8132617,
  abstract     = {Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells.},
  author       = {Drennan, Michael and Govindarajan, Srinath and Verheugen, Eveline and Coquet, Jonathan and Staal, Jens and Mc Guire, Conor and Taghon, Tom and Leclercq, Georges and Beyaert, Rudi and van Loo, Geert and Lambrecht, Bart and Elewaut, Dirk},
  issn         = {0022-1007},
  journal      = {JOURNAL OF EXPERIMENTAL MEDICINE},
  language     = {eng},
  number       = {10},
  pages        = {1973--1981},
  title        = {NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNF AIP3/A20},
  url          = {http://dx.doi.org/10.1084/jem.20151065},
  volume       = {213},
  year         = {2016},
}

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