Chromatin assembly factor 1B critically controls the early development but not function acquisition of invariant natural killer T cells in mice. Issue 7 (20th May 2021)

• Record Type: Journal Article
• Authors: Xu, Yu; Ma, Junwei; Luo, Haorui; Shi, Yaohuang; Liu, Haifeng; Sun, Ao; Xu, Chenqi; Ji, Hongbin; Liu, Xiaolong
• Is Part Of: European journal of immunology. Volume 51:Issue 7(2021)
• Page Start: 1698
• Page End: 1714
• Publication Date: 2021-05-20
• Subjects: CHAF1b -- Function acquisition -- iNKT cell development -- TCR; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202049074
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: CD4 + CD8 + double‐positive thymocytes give rise to both conventional TCRαβ + T cells and invariant natural killer T cells (iNKT cells), but these two kinds of cells display different characteristics. The molecular mechanism underlying iNKT cell lineage development and function acquisition remain to be elucidated. We show that the loss of chromatin assembly factor 1B (CHAF1b) maintains the normal development of conventional TCRαβ + T cells but severely impairs early development of iNKT cells. This dysregulation is accompanied by the impairment in chromatin activation and gene transcription at Vα14 ‐ Jα18 locus. Notably, ectopic expression of a Vα14‐Jα18 TCR rescues Chaf1b ‐deficient iNKT cell developmental defects. Moreover, cytokine secretion and antitumor activity are substantially maintained in Vα14‐Jα18 TCR transgene‐rescued Chaf1b ‐deficient iNKT cells. Our study identifies CHAF1b as a critical factor that controls the early development but not function acquisition of iNKT cells via lineage‐ and stage‐specific regulation. Abstract : CHAF1b, one subunit of the chromatin assembly factor‐1 complex, controls early development of iNKT cells by regulation of Vα14‐Jα18 TCR expression with no influences of conventional TCRαβ + T‐cell development and function acquisition of iNKT cells. These results implicate the lineage‐ and stage‐specific function of CHAF1b in iNKT cell development.