Transcriptome and chromatin landscape of iNKT cells are shaped by subset differentiation and antigen exposure

Nat Commun. 2021 Mar 4;12(1):1446. doi: 10.1038/s41467-021-21574-w.

Abstract

Invariant natural killer T cells (iNKT cells) differentiate into thymic and peripheral NKT1, NKT2 and NKT17 subsets. Here we use RNA-seq and ATAC-seq analyses and show iNKT subsets are similar, regardless of tissue location. Lung iNKT cell subsets possess the most distinct location-specific features, shared with other innate lymphocytes in the lung, possibly consistent with increased activation. Following antigenic stimulation, iNKT cells undergo chromatin and transcriptional changes delineating two populations: one similar to follicular helper T cells and the other NK or effector like. Phenotypic analysis indicates these changes are observed long-term, suggesting that iNKT cells gene programs are not fixed, but they are capable of chromatin remodeling after antigen to give rise to additional subsets.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Chromatin / genetics
  • Female
  • Lung / cytology*
  • Lung / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / cytology*
  • Natural Killer T-Cells / immunology
  • T Follicular Helper Cells / cytology*
  • T Follicular Helper Cells / immunology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Transcriptome / genetics

Substances

  • Chromatin