In:
European Journal of Immunology, Wiley, Vol. 52, No. 11 ( 2022-11), p. 1789-1804
Abstract:
Thymic epithelial cells (TECs) are important for T cell development and immune tolerance establishment. Although comprehensive molecular regulation of TEC development has been studied, the role of transport protein particle complexes (Trappcs) in TECs is not clear. Using TEC‐specific homozygous or heterozygous Trappc1 deleted mice model, we find that Trappc1 deficiency cause severe thymus atrophy with decreased cell number and blocked maturation of TECs. Mice with a TEC‐specific Trappc1 deletion show poor thymic T cell output and have a greater percentage of activated/memory T cells, suffered from spontaneous autoimmune disorders. Our RNA‐seq and molecular studies indicated that the decreased endoplasmic reticulum (ER) and Golgi apparatus, enhanced unfolded protein response (UPR) and subsequent Atf4‐CHOP‐mediated apoptosis, and reactive oxygen species (ROS)‐mediated ferroptosis coordinately contributed to the reduction of Trappc1‐deleted TECs. Additionally, reduced Aire + mTECs accompanied by the decreased expression of Irf4, Irf8, and Tbx21 in Trappc1 deficiency mTECs, may further coordinately block the tissue‐restricted antigen expression. In this study, we reveal that Trappc1 plays an indispensable role in TEC development and maturation and provide evidence for the importance of inter‐organelle traffic and ER homeostasis in TEC development.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.202249915
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
1491907-2
