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hnRNPA1 enhances FOXP3 stability to promote the differentiation and functions of regulatory T cells
Author(s) -
Liu Xu,
Tian Na,
Huang Qianru,
Xu Zhan,
Cheng Hao,
Liu Xinnan,
Li Dan,
Liang Rui,
Li Bin,
Dai Xueyu
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14142
Subject(s) - foxp3 , gene knockdown , microbiology and biotechnology , transcription factor , phosphorylation , ubiquitin ligase , phenotype , ubiquitin , chemistry , biology , immunology , cell culture , immune system , gene , genetics , biochemistry
Regulatory T cells (Tregs) are indispensable for the maintenance of immunological self‐tolerance and homeostasis. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is required for optimal Treg induction. Here, we reveal that human‐induced Tregs (iTregs) lacking hnRNPA1 show reduced expression of the transcription factor FOXP3, increased ubiquitination level of FOXP3, and impaired suppressive abilities. Human naïve CD4 T cells with hnRNPA1 knockdown show a decreased Treg differentiation ratio. hnRNPA1 could interact with FOXP3 as well as with the E3 ligase Stub1. The phosphorylation at hnRNPA1 S199 could increase both interactions. The overexpression of FOXP3 in Tregs containing shhnRNPA1 could not recover the phenotype caused by hnRNPA1 knockdown. Therefore, there might be multiple essential pathways regulated by hnRNPA1 in Tregs. In conclusion, we present a new role of hnRNPA1 in promoting Treg function, indicating it as a promising target for tumor therapies.