Commentary: Is the IMQ Mouse Model Hindering Psoriasis Research?

A perspective piece in the Journal of Investigative Dermatology takes a criticial look at the imiquimod (IMQ) mouse model, suggesting its unversality and commonality may be impeding translational progress in psoriasis research.

"Once hailed as a breakthrough in psoriasis research, the IMQ mouse model is now overused, inconsistently applied, and increasingly disconnected from human disease," the authors wrote. "Nearly a decade after our initial critique, the field remains reliant on a tool that models acute, innate inflammation rather than chronic, adaptive immunity."

The authors went on to highlight while the inexpensive model that reproduces features such as acanthosis, neutrophilic infiltrates, and IL-23/IL-17 pathway activation, IMQ-induced dermatitis became widely adopted after 2009. However, the authors wrote that the model primarily reflects acute, innate immune activation rather than chronic, T cell–driven psoriasis.

In a review of the 100 most recent English-language IMQ studies (June 2024–May 2025), investigators identified 39 distinct protocols varying in dose, duration, controls, and mouse strain. Fewer than 20% of studies included both sexes, and histologic assessment was frequently suboptimal. Subjective “PASI-like” scoring systems and inconsistent imaging further limited reproducibility.

The authors also cite transcriptomic divergence between IMQ-treated mouse skin and human psoriatic lesions, including poor alignment in genes linked to chronic adaptive immunity and barrier function. Notably, IL-17A or IL-23 blockade produces only partial suppression in IMQ models, whereas targeted inhibition in patients leads to near-complete histologic normalization.

"We issued a caution in 2016," the authors wrote. "The evidence in 2025 forces that caution into a call to action.I f psoriasis research is to move forward, it must be willing to leave behind the tools that no longer serve it."

Source: Smith C, et al. JID. 2026. doi:10.1016/j.jid.2025.09.005