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

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.