Histone deacetylase 3 is required for iNKT cell development

• Published in: Scientific reports Vol. 7; no. 1; pp. 5784 - 13
• Main Authors: Thapa, Puspa, Romero Arocha, Sinibaldo, Chung, Ji Young, Sant'Angelo, Derek B, Shapiro, Virginia Smith
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.07.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Apoptosis; Autophagy; Bcl-2 protein; Bcl-x protein; Cell death; Cell Differentiation; Cell Survival; Clonal deletion; Cytokines - metabolism; Gene Deletion; Histone deacetylase; Histone Deacetylases - deficiency; Histone Deacetylases - metabolism; Lymphocytes T; Mice, Inbred C57BL; Mice, Knockout; Natural killer cells; Natural Killer T-Cells - physiology; Nutrients; Phagocytosis; T cell receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-06102-5

NKT cells are a distinct subset that have developmental requirements that often differ from conventional T cells. Here, we show that NKT-specific deletion of Hdac3 results in a severe reduction in the number of iNKT cells, particularly of NKT1 cells. In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 cells. Hdac3-deficient iNKT cells have increased cell death that is not rescued by transgenic expression of Bcl-2 or Bcl-xL. Hdac3-deficient iNKT cells have less Cyto-ID staining and lower LC3A/B expression, indicative of reduced autophagy. Interestingly, Hdac3-deficient iNKT cells also have lower expression of the nutrient receptors GLUT1, CD71 and CD98, which would increase the need for autophagy when nutrients are limiting. Therefore, Hdac3 is required for iNKT cell development and differentiation.