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Thymic mimetic cells function beyond self-tolerance
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Journal Article
Thymic mimetic cells function beyond self-tolerance
2023
Overview
Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection
1
.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells
2
–
7
. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require
Insm1
for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require
Spib
for their development and are essential for the generation of thymic IgA
+
plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations.
Multiomic analyses of mouse thymic epithelial cells identify several unconventional subsets that are mimetics of various populations of terminally differentiated parenchymal cells and provide insights into their development, molecular features and function.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/106
/ 13/21
/ 13/31
/ 13/51
/ 14
/ 14/1
/ 14/19
/ 14/63
/ 38
/ 38/77
/ 38/90
/ 38/91
/ 59
/ 82
/ Animals
/ Cloning
/ DNA-Binding Proteins - metabolism
/ Epithelial Cells - metabolism
/ Genes
/ Ghrelin
/ Humanities and Social Sciences
/ Mice
/ Myocytes
/ Science
/ Self
/ T-Lymphocytes - classification
/ Thymus
