RNA Helicase DDX21 Controls CD4 + T Cell Proliferation and Promotes Inflammatory Bowel Disease via Translational Control
Source abstract
Abstract
ABSTRACT Inflammatory bowel disease (IBD) is characterized by dysregulated T cell responses. RNA helicases, including DExD‐box helicase 21 (DDX21), are pivotal in RNA metabolism, but their role in T cell‐mediated pathology during IBD remains unclear. Here, we demonstrate that DDX21 expression in CD4 + T cells correlates with cell cycle and translation pathways in IBD‐affected tissues. Conditional deletion of Ddx21 in mouse T cells disrupts T cell homeostasis and impairs cell proliferation. Consequently, Ddx21 –deficient CD4 + T cells exhibit resistance to inducing adoptive transfer colitis, with recipients showing reduced T cell infiltration compared to wild‐type (WT) counterparts. Mechanistically, DDX21 ensures ribosome biogenesis after T cell activation and facilitates mRNA translation of Transcription factor dp‐1 (TFDP1), a transcription factor critical for cell cycle progression. Given this dependence on ribosome biogenesis, pharmacological targeting of this pathway via KU55933—an inhibitor of ribosome synthesis‐related signaling—recapitulated the protective effects of DDX21 loss: KU55933 alleviated dextran sulfate sodium (DSS)‐induced colitis in mice and attenuated pathogenic CD4 + T cell expansion. Our findings establish DDX21 as a key regulator of T cell proliferation and highlight its potential as a therapeutic target for IBD and other autoimmune disorders.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: RNA Research and Splicing · RNA modifications and cancer · RNA regulation and disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Geriatrics Medical Center on Aging of Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
Center For Immune‐Related Diseases At Shanghai Institute of Immunology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
Shanghai Jiao Tong University School of Medicine‐Yale Institute For Immune Metabolism Shanghai Jiao Tong University School of Medicine Shanghai China
School of Biological Science The University of Manchester Manchester UK
Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
Department of Urology Shanghai Tenth People's Hospital Tongji University Shanghai China
Urologic Cancer Institute School of Medicine Tongji University Shanghai China
Institute For Immunology and Pathogenesis Chongqing Medical University Chongqing China
Institute of Frontier Technologies and Interdisciplinary Research Chongqing Medical University Chongqing China
Department of Pathology The First Affiliated Hospital of Chongqing Medical University Chongqing China
Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai China
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China · Chongqing Municipal Science and Technology Bureau · Fundamental Research Funds for the Central Universities · China Postdoctoral Science Foundation
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