1052-The GGPP-RAB35 Axis in Tfh Cell Regulation

The research identifies the mevalonate (MVA) pathway and its derivative, GGPP, as critical regulators of T follicular helper (Tfh) cell differentiation and function. Scientists discovered that the enzyme GGTase II uses GGPP to modify RAB35 proteins, a process essential for recycling the CXCR5 receptor to the cell surface so Tfh cells can interact with B cells. This metabolic axis is driven by T cell receptor (TCR) signaling and is found to be overactive in patients with systemic lupus erythematosus (SLE). By applying pitavastatin, the researchers were able to block this pathway, reducing the surface expression of key functional molecules and alleviating autoimmune disease severity in animal models. The study concludes that targeting this specific metabolic vulnerability offers a promising therapeutic strategy for treating Tfh-mediated autoimmunity. These findings also suggest that dietary intake of GGPP or statin use could significantly influence vaccine efficacy and humoral immune responses.

References:

• Wang L, Jiang J, Yin H, et al. Modulation of the mevalonate pathway by TCR engagement regulates T follicular helper cell generation in homeostasis and autoimmunity[J]. Immunity, 2026.