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

• Published in: Nature communications Vol. 12; no. 1; pp. 1446 - 14
• Main Authors: Murray, Mallory Paynich, Engel, Isaac, Seumois, Grégory, Herrera-De la Mata, Sara, Rosales, Sandy Lucette, Sethi, Ashu, Logandha Ramamoorthy Premlal, Ashmitaa, Seo, Goo-Young, Greenbaum, Jason, Vijayanand, Pandurangan, Scott-Browne, James P., Kronenberg, Mitchell
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/91; 631/250; 631/250/1619; 631/250/2152/1566; 631/250/2504/2506; Animals; Antigens; Cell differentiation; Cell Differentiation - immunology; Chromatin - genetics; Chromatin remodeling; Female; Gene expression; Humanities and Social Sciences; Invariants; Lung - cytology; Lung - immunology; Lungs; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Natural killer cells; Natural Killer T-Cells - cytology; Natural Killer T-Cells - immunology; Populations; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Stimulation; T Follicular Helper Cells - cytology; T Follicular Helper Cells - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; Thymus; Thymus Gland - cytology; Thymus Gland - immunology; Transcription; Transcriptome - genetics; Transcriptomes; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21574-w

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. Invariant natural killer T cells are known to be composed of a number of phenotypic and functionally distinct populations. Here the authors use transcriptomic and epigenomic analysis to further characterize the peripheral iNKT compartment before and after antigenic stimulation.