DOI: 10.1093/intimm/dxad049 ISSN: 1460-2377

ACC1-mediated fatty acid biosynthesis intrinsically controls thymic iNKT cell development

Toshio Kanno, Keisuke Miyako, Takeru Endo, Satoru Yokoyama, Hikari K Asou, Kazuko Yamada, Osamu Ohara, Toshinori Nakayama, Motoko Y Kimura, Yusuke Endo
  • Immunology
  • General Medicine
  • Immunology and Allergy


To meet the energetic requirements associated with activation, proliferation and survival, T cells switch their metabolic signatures from energetically quiescent to activated. However, little is known about the role of metabolic pathway controlling the development of invariant natural killer T (iNKT) cells. In the present study, we found that acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme for fatty acid biosynthesis pathway, plays an essential role in the development of iNKT cells in the thymus. Mice lacking T-cell specific ACC1 showed reduced number of iNKT cells with an increased proportion of iNKT cells at immature stages 0 and 1. Furthermore, mixed bone marrow (BM) chimera experiments revealed that T-cell-intrinsic ACC1 expression was selectively important for the development of thymic iNKT cells, especially for the differentiation of NKT1 cell subset. Our single-cell RNA-sequencing (scRNA-seq) data and functional analysis demonstrated that ACC1 is responsible for survival of developing iNKT cells. Thus, these findings highlighted a novel role of ACC1 in controlling thymic iNKT cell development mediated by the control of cell survival.

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