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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\u2010specific 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\u2010specific 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\u2010seq and molecular studies indicated that the decreased endoplasmic reticulum (ER) and Golgi apparatus, enhanced unfolded protein response (UPR) and subsequent Atf4\u2010CHOP\u2010mediated apoptosis, and reactive oxygen species (ROS)\u2010mediated ferroptosis coordinately contributed to the reduction of Trappc1\u2010deleted TECs. Additionally, reduced Aire\n                    <jats:sup>+<\/jats:sup>\n                    mTECs accompanied by the decreased expression of Irf4, Irf8, and Tbx21 in Trappc1 deficiency mTECs, may further coordinately block the tissue\u2010restricted 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\u2010organelle traffic and ER homeostasis in TEC development.\n                  <\/jats:p>","DOI":"10.1002\/eji.202249915","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T02:05:29Z","timestamp":1659233129000},"page":"1789-1804","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Trappc1 deficiency impairs thymic epithelial cell development by breaking endoplasmic reticulum homeostasis"],"prefix":"10.1002","volume":"52","author":[{"given":"Xue","family":"Dong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing 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