2023-09-06 カリフォルニア大学リバーサイド校(UCR)
◆研究により、これらの新しいM細胞が腸管や気道で見られるM細胞と非常に類似していることが示され、その機能的違いが研究の対象となっています。胸腺は免疫システムの発達において重要な役割を果たすため、新しく発見されたM細胞は免疫システムの理解に新たな洞察を提供する可能性があります。
<関連情報>
- https://news.ucr.edu/articles/2023/09/06/study-reports-discovery-new-cell-type-thymus
- https://www.nature.com/articles/s41586-023-06512-8
胸腺模倣細胞は自己寛容を超えて機能する Thymic mimetic cells function beyond self-tolerance
Tal Givony,Dena Leshkowitz,Diana Del Castillo,Shir Nevo,Noam Kadouri,Bareket Dassa,Yael Gruper,Razi Khalaila,Osher Ben-Nun,Tom Gome,Jan Dobeš,Shifra Ben-Dor,Merav Kedmi,Hadas Keren-Shaul,Rebecca Heffner-Krausz,Ziv Porat,Ofra Golani,Yoseph Addadi,Ori Brenner,David D. Lo,Yael Goldfarb & Jakub Abramson
Nature Published:06 September 2023
DOI:https://doi.org/10.1038/s41586-023-06512-8
Abstract
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 selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2,3,4,5,6,7. 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.
