Emerging therapeutic strategies for SLE extend beyond B cell depletion to target CD4 follicular helper T (Tfh) cells: E4BP4 inhibits Tfh differentiation by repressing BCL-6 transcription via recruitment of HDAC1 and EZH2, while impaired E4BP4 function and IFN-I–driven IL-21/IFN-γ production promote Tfh expansion and autoreactive B cell responses, supporting Tfh-directed CAR-T approaches (54, 55). This evidence concerns the gene IL21 and systemic lupus erythematosus.