Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells

Dinh, Xuyen T., Stanley, Dragana, Smith, Letitia D., Moreau, Morgane, Berzins, Stuart P., Gemiarto, Adrian, Baxter, Alan G., and Jordan, Margaret A. (2021) Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells. Scientific Reports, 11. 23650.

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Abstract

iNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development and separates, the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment.

Item ID: 71233
Item Type: Article (Research - C1)
ISSN: 2045-2322
Keywords: immature iNKT cells; lineage commitment; transcriptional events; rodent; autoimmunity; tolerance; suppression; anergy
Copyright Information: Open Access Tis article is licensed under a Creative Commons Attribution 4.0 International license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2021
Funders: Australian Development Scholarship, MS Research Australia, NHMRC Early Career Fellowship, NHMRC Senior Research Fellowship, NHMRC
Research Data: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE106720
Date Deposited: 18 Jan 2022 04:44
FoR Codes: 31 BIOLOGICAL SCIENCES > 3105 Genetics > 310507 Genetic immunology @ 40%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310202 Biological network analysis @ 30%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 30%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 50%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 50%
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