Trappc1 is essential for naive T cell survival

T lymphocytes are pivotal in adaptive immunity. The role of trafficking protein particle complex (TRAPPC) in regulating T cell development and homeostasis are unknown. Using CD4cre-Trappc1flox/flox (Trappc1 cKO) mice, we found that Trappc1 deficiency in T cells significantly decreased cell number of naïve T cells in the periphery, whereas thymic T cell development in Trappc1 cKO mice was identical as in WT mice. In the culture assays and mouse models with adoptive transfer of the sorted WT (CD45.1+CD45.2+) and Trappc1 cKO naive T cells (CD45.2+) to CD45.1+ syngeneic mice, Trappc1-deficienct naive T cells showed significantly reduced survival ability compared with WT cells. RNA-seq and molecular studies showed that Trappc1 deficiency in naive T cells reduced protein transport from the endoplasmic reticulum to Golgi apparatus, enhanced unfolded protein responses, increased P53 transcription, intracellular Ca2+, Atf4-CHOP, oxidative phosphorylation and lipid peroxide accumulation, and subsequently led to ferroptosis. Overall design: Naive CD4+ T cells and naive CD8+ T cells were sorted by CD4+/CD8+CD62L+CD44low from the mLNs and spleens of 4 weeks old WT and CD4-cre Trappc1 cKO mice. The total RNA of the sorted naive CD4+ T cells and naive CD8+ T cells were extracted using TRIzol reagent (Thermo Fisher, 15596018), and sequencing were done by the Annoroad Gene Technology Co., Ltd (Beijing). Differential expressed genes were carried out by DEseq2 software38. KEGG pathway enrichment was performed by KOBAS 3.0.28 (http://kobas.cbi.pku.edu.cn/)37,59. Protein and protein interaction network were analyzed by String (https://string-db.org/) and visualized by Cytoscape60.