Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Department of Pediatrics, Rutgers Robert Wood Johnson Medical School and The Children's Health Institute of New Jersey, 89 French Street, Room 4273, New Brunswick, NJ, 08901, USA.
Sci Rep. 2017 Jul 19;7(1):5784. 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.
NKT 细胞是一个独特的亚群，其发育需求通常与传统 T 细胞不同。在这里，我们表明，NKT 细胞特异性缺失 Hdac3 会导致 iNKT 细胞数量严重减少，尤其是 NKT1 细胞。此外，Hdac3 缺陷的 NKT2 和 NKT17 细胞产生的细胞因子减少。Hdac3 缺陷的 iNKT 细胞死亡增加，而转 Bcl-2 或 Bcl-xL 基因表达不能挽救这种增加。Hdac3 缺陷的 iNKT 细胞 Cyto-ID 染色减少，LC3A/B 表达降低，表明自噬减少。有趣的是，Hdac3 缺陷的 iNKT 细胞对营养受体 GLUT1、CD71 和 CD98 的表达也降低，这会增加在营养物质有限时自噬的需求。因此，Hdac3 是 iNKT 细胞发育和分化所必需的。
