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Cells
Volume 13
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10.3390/cells13121073
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Open AccessArticle
by Tzong-Shyuan Tai SciProfiles Scilit Preprints.org Google Scholar Huang-Yu Yang SciProfiles Scilit Preprints.org Google Scholar Wan-Chu Chuang SciProfiles Scilit Preprints.org Google Scholar Yu-Wen Huang SciProfiles Scilit Preprints.org Google Scholar I-Cheng Ho SciProfiles Scilit Preprints.org Google Scholar Ching-Chung Tsai SciProfiles Scilit Preprints.org Google Scholar Ya-Ting Chuang SciProfiles Scilit Preprints.org Google Scholar 
Tzong-Shyuan TaiHuang-Yu YangWan-Chu ChuangYu-Wen Huang
, I-Cheng HoChing-Chung Tsai and Ya-Ting Chuang
1
Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
2
Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
3
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
4
Advanced Immunology Laboratory, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
5
Department of Medical Research, National Taiwan University Hospital, Taipei 10002, Taiwan
6
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital, 60 Fenwood Road, Boston, MA 02115, USA
7
Harvard Medical School, 60 Fenwood Road, Boston, MA 02115, USA
8
Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung City 82445, Taiwan
9
School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan
*
Authors to whom correspondence should be addressed.
Cells 2024, 13(12), 1073; https://doi.org/10.3390/cells13121073
Submission received: 21 May 2024 / Revised: 18 June 2024 / Accepted: 19 June 2024 / Published: 20 June 2024
(This article belongs to the Collection Feature Papers in ‘Cellular Immunology’)
Abstract
While the transcription factor GATA-3 is well-established for its crucial role in T cell development, its specific influence on invariant natural killer T (iNKT) cells remains relatively unexplored. Using flow cytometry and single-cell transcriptomic analysis, we demonstrated that GATA-3 deficiency in mice leads to the absence of iNKT2 and iNKT17 cell subsets, as well as an altered distribution of iNKT1 cells. Thymic iNKT cells lacking GATA-3 exhibited diminished expression of PLZF and T-bet, key transcription factors involved in iNKT cell differentiation, and reduced production of Th2, Th17, and cytotoxic effector molecules. Single-cell transcriptomics revealed a comprehensive absence of iNKT17 cells, a substantial reduction in iNKT2 cells, and an increase in iNKT1 cells in GATA-3-deficient thymi. Differential expression analysis highlighted the regulatory role of GATA-3 in T cell activation signaling and altered expression of genes critical for iNKT cell differentiation, such as Icos, Cd127, Eomes, and Zbtb16. Notably, restoration of Icos, but not Cd127, expression could rescue iNKT cell development in GATA-3-deficient mice. In conclusion, our study demonstrates the pivotal role of GATA-3 in orchestrating iNKT cell effector lineage differentiation through the regulation of T cell activation pathways and Icos expression, providing insights into the molecular mechanisms governing iNKT cell development and function.
Keywords: iNKT cells; single-cell RNA sequencing; GATA-3; Icos; CD127
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MDPI and ACS Style
Tai, T.-S.; Yang, H.-Y.; Chuang, W.-C.; Huang, Y.-W.; Ho, I.-C.; Tsai, C.-C.; Chuang, Y.-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells 2024, 13, 1073. https://doi.org/10.3390/cells13121073
AMA Style
Tai T-S, Yang H-Y, Chuang W-C, Huang Y-W, Ho I-C, Tsai C-C, Chuang Y-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells. 2024; 13(12):1073. https://doi.org/10.3390/cells13121073
Chicago/Turabian Style
Tai, Tzong-Shyuan, Huang-Yu Yang, Wan-Chu Chuang, Yu-Wen Huang, I-Cheng Ho, Ching-Chung Tsai, and Ya-Ting Chuang. 2024. "ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation" Cells 13, no. 12: 1073. https://doi.org/10.3390/cells13121073
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
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MDPI and ACS Style
Tai, T.-S.; Yang, H.-Y.; Chuang, W.-C.; Huang, Y.-W.; Ho, I.-C.; Tsai, C.-C.; Chuang, Y.-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells 2024, 13, 1073. https://doi.org/10.3390/cells13121073
AMA Style
Tai T-S, Yang H-Y, Chuang W-C, Huang Y-W, Ho I-C, Tsai C-C, Chuang Y-T. ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation. Cells. 2024; 13(12):1073. https://doi.org/10.3390/cells13121073
Chicago/Turabian Style
Tai, Tzong-Shyuan, Huang-Yu Yang, Wan-Chu Chuang, Yu-Wen Huang, I-Cheng Ho, Ching-Chung Tsai, and Ya-Ting Chuang. 2024. "ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation" Cells 13, no. 12: 1073. https://doi.org/10.3390/cells13121073
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
Cells, EISSN 2073-4409, Published by MDPI
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