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Peer-reviewedCC BY 4.0Frontiers in Immunology

Research progress of the DExD/H-Box RNA helicase family in T cell immune responses

  • Wenlin Li1,2
  • Kun Wu1,2,3
  • Tiancheng Zhao1,2
  • Wenbo Yang1,2
  • Yongjie Zhang1,2
  • Zhao Zhao1,2
  • Jiankang Dong1,2
  • Yujie Yang1,2
  • He Li1,2,3
  • Jianfei Wang1,2
  • Weiyu Zhang1,2
  • Qiang Wang1,2
  1. 1Department of Urology, Peking University People’s Hospital
  2. 2Peking University Institute of Organ Transplantation
  3. 3Hebei North University
Open at sourceDOICite

Abstract

T-cell immunity orchestrates host defense against pathogens, tumor surveillance, and autoimmune tolerance, yet the full repertoire of post-transcriptional regulators shaping T-cell fate remains incompletely defined. The DExD/H-box RNA helicase family, best known for canonical RNA-metabolic and nucleic-acid-sensing activities, has emerged as multifaceted modulators governing multiple key steps of T-cell biology. Beyond acting as pattern-recognition sensors in antigen-presenting cells, these helicases exert cell-intrinsic control over T-cell receptor signaling, thymic development, helper-subset polarization, cytotoxic CD8 ⁺ T-cell effector-memory programming, and regulatory T-cell lineage commitment via chromatin remodeling, pre-mRNA splicing, translational control and transposable-element homeostasis. Accumulating pre-clinical evidence highlights their potential translational value as biomarkers or therapeutic targets, pending further validation for autoimmunity, infection, cancer and transplant rejection. Nevertheless, major gaps persist, including poorly resolved T-cell-specific functions for most helicase paralogs, obscure molecular underpinnings of their non-canonical activities, and challenges in achieving isoform-selective pharmacological targeting. Here we synthesize current mechanistic insights of DExD/H-box helicases in T-cell immunity, discuss their translational opportunities, and outline critical outstanding questions to guide future functional and therapeutic investigations.

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Cite

BibTeXRIS
BibTeX
@article{li2026research,
  title = {{Research progress of the DExD/H-Box RNA helicase family in T cell immune responses}},
  author = {Wenlin Li and Kun Wu and Tiancheng Zhao and Wenbo Yang and Yongjie Zhang and Zhao Zhao and Jiankang Dong and Yujie Yang and He Li and Jianfei Wang and Weiyu Zhang and Qiang Wang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.2005330},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2005330/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Research progress of the DExD/H-Box RNA helicase family in T cell immune responses
AU  - Wenlin Li
AU  - Kun Wu
AU  - Tiancheng Zhao
AU  - Wenbo Yang
AU  - Yongjie Zhang
AU  - Zhao Zhao
AU  - Jiankang Dong
AU  - Yujie Yang
AU  - He Li
AU  - Jianfei Wang
AU  - Weiyu Zhang
AU  - Qiang Wang
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.2005330
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2005330/full
AB  - T-cell immunity orchestrates host defense against pathogens, tumor surveillance, and autoimmune tolerance, yet the full repertoire of post-transcriptional regulators shaping T-cell fate remains incompletely defined. The DExD/H-box RNA helicase family, best known for canonical RNA-metabolic and nucleic-acid-sensing activities, has emerged as multifaceted modulators governing multiple key steps of T-cell biology. Beyond acting as pattern-recognition sensors in antigen-presenting cells, these helicases exert cell-intrinsic control over T-cell receptor signaling, thymic development, helper-subset polarization, cytotoxic CD8 ⁺ T-cell effector-memory programming, and regulatory T-cell lineage commitment via chromatin remodeling, pre-mRNA splicing, translational control and transposable-element homeostasis. Accumulating pre-clinical evidence highlights their potential translational value as biomarkers or therapeutic targets, pending further validation for autoimmunity, infection, cancer and transplant rejection. Nevertheless, major gaps persist, including poorly resolved T-cell-specific functions for most helicase paralogs, obscure molecular underpinnings of their non-canonical activities, and challenges in achieving isoform-selective pharmacological targeting. Here we synthesize current mechanistic insights of DExD/H-box helicases in T-cell immunity, discuss their translational opportunities, and outline critical outstanding questions to guide future functional and therapeutic investigations.
SN  - 1664-3224
ER  -