Expression of the transcription factor Klf6 by thymic epithelial cells is required for thymus development-Reference-Cited by-同舟云学术

Expression of the transcription factor Klf6 by thymic epithelial cells is required for thymus development

Published:2023-11-17 Issue:46 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Malin Justin¹^ORCID,Martinez-Ruiz Gustavo Ulises¹²³^ORCID,Zhao Yongge¹^ORCID,Shissler Susannah C.¹^ORCID,Cowan Jennifer E.¹⁴,Ding Yi¹^ORCID,Morales-Sanchez Abigail¹³,Ishikawa Masaki¹⁵,Lavaert Marieke¹,Das Arundhoti¹,Butcher Donna⁶^ORCID,Warner Andrew C.⁶^ORCID,Kallarakal Melissa¹,Chen Jingqiu⁷⁸,Kedei Noemi⁷,Kelly Michael⁹^ORCID,Brinster Lauren R.¹⁰,Allman David⁵,Bhandoola Avinash¹^ORCID

Affiliation:

1. Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

2. Research Division, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.

3. Children’s Hospital Federico Gomez, Mexico City, Mexico.

4. Institute of Immunity and Transplantation, University College London, London, UK.

5. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

6. Molecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

7. Office of Science and Technology Resources, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

8. ACROBiosystems, Newark, DE, USA.

9. Single Cell Analysis Facility, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

10. Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, MD, USA.

Abstract

Thymic epithelial cells (TEC) control T cell development and play essential roles in establishing self-tolerance. By using Foxn1-Cre –driven ablation of Klf6 gene in TEC, we identified Klf6 as a critical factor in TEC development. Klf6 deficiency resulted in a hypoplastic thymus—evident from fetal stages into adulthood—in which a dramatic increase in the frequency of apoptotic TEC was observed. Among cortical TEC (cTEC), a previously unreported cTEC population expressing the transcription factor Sox10 was relatively expanded. Within medullary TEC (mTEC), mTEC I and Tuft-like mTEC IV were disproportionately decreased. Klf6 deficiency altered chromatin accessibility and affected TEC chromatin configuration. Consistent with these defects, naïve conventional T cells and invariant natural killer T cells were reduced in the spleen. Late stages of T cell receptor–dependent selection of thymocytes were affected, and mice exhibited autoimmunity. Thus, Klf6 has a prosurvival role and affects the development of specific TEC subsets contributing to thymic function.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adg8126

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