Acitretin

Acitretin, an approved retinoid, inhibited BK polyomavirus (BKPyV) replication in primary human renal proximal tubular epithelial cells (EC50 0.64 μM, selectivity index 250) and in urothelial cells, but not in COS‑7 cells that constitutively express SV40 large T antigen. The effect required early addition (up to 12 hours post‑infection) and involved reduced large T‑antigen transcription and protein expression. Other retinoic acid agonists and the RAR/RXR antagonist RO41‑5253 also inhibited BKPyV, suggesting a novel, undefined mechanism. Acitretin reaches inhibitory concentrations systemically, supporting clinical repurposing for BKPyV‑associated diseases.

Fig. 1 Acitretin does not inhibit BKPyV replication by activating type I interferons. (Wu Z, et al., 2021)

Psoriasis patients showed expanded numbers of myeloid‑derived suppressor cells (MDSCs) and monocytic‑MDSCs (M‑MDSCs) in blood and skin lesions, correlating with disease severity. Acitretin reduced MDSC numbers in patients and in an IMQ‑induced psoriasis mouse model. Mechanistically, acitretin increased glutathione synthase expression and glutathione accumulation in MDSCs, promoting their differentiation into CD206⁺ M2 macrophages and CD11c⁺MHC‑II⁺ dendritic cells. Interrupting GSH synthesis abrogated this effect. ERK1/2 activation regulated GSS expression. This novel immunomodulatory mechanism explains acitretin’s efficacy in psoriasis beyond its direct action on keratinocytes.

Fig. 2 MDSCs and M-MDSCs expansion was found in the peripheral blood and skin lesions of psoriasis patients. (Liu P, et al., 2021)