The imiquimod (IMQ)-induced psoriasis model is widely used in preclinical dermatology research due to its ability to rapidly generate localized skin inflammation that resembles key features of human plaque psoriasis. However, mounting evidence suggests that not all mouse strains respond to IMQ in the same way—an important consideration when designing efficacy studies for anti-inflammatory or immunomodulatory compounds.
How IMQ Works and Why It’s Used in Psoriasis Research
IMQ is a Toll-like receptor 7/8 (TLR7/8) agonist that, when applied topically, initiates a localized inflammatory response through activation of the innate immune system, including the IL-23/IL-17 cytokine axis, which plays a central role in the pathogenesis of psoriasis. In the IMQ-induced mouse model, IMQ stimulates dendritic cells to produce IL-23, which in turn activates dermal γδ T cells, the predominant source of IL-17A, IL-17F and IL-22 in this model (1-3). These cytokines act directly on keratinocytes, driving hyperproliferation, impaired differentiation, and the release of additional pro-inflammatory mediators. The result is a robust inflammatory cascade characterized by erythema, scaling, and neutrophil infiltration (4-5).
While the IMQ model effectively displays many aspects of psoriasis-like inflammation, the strength and character of this response can vary depending on the genetic background of the animals used. A study by Swindell et al. (2017) examined gene expression profiles across multiple mouse strains treated with IMQ. The researchers found that only C57BL/6 mice exhibited a transcriptional signature closely resembling those observed in human psoriatic lesions, while other strains, like BALB/c, showed responses more consistent with general inflammation or wound healing (6). These findings raised important considerations for model selection and study interpretation in preclinical drug development, particularly for therapies targeting immune pathways. To build on this work and evaluate its implications for translational research, scientists at Inotiv conducted a follow-up strain characterization study comparing responses to IMQ in BALB/c and C57BL/6 mice. The goal was to better understand how strain-dependent differences might influence disease features and treatment outcomes in the IMQ-induced psoriasis model.
Study Overview
In this study, BALB/c and C57BL/6 mice received daily topical applications of 5% IMQ cream to the dorsal skin for 7 days to induce psoriasis-like inflammation. Terminal tissue and plasma samples were collected at multiple time points to characterize the resulting immune responses. Cytokine and chemokine profiling was performed using the Meso Scale Discovery (MSD) platform, and immune cell populations were analyzed by flow cytometry. The results revealed distinct differences in disease severity, immune responses, and treatment outcomes between the two strains.
C57BL/6 Mice: Mild Disease with Complex Immune Response
C57BL/6 mice developed robust psoriasis-like disease in response to IMQ treatment, although the overall severity was lower compared to BALB/c mice, consistent with previously published data (7). Histopathological analysis showed more pronounced epidermal hyperplasia but with relatively less inflammation and hyperkeratosis. Despite these differences, summed histopathology scores in untreated groups were generally similar between strains.
Interestingly, our findings differed from earlier transcriptomic studies that demonstrated a psoriasis-like gene expression signature in C57BL/6 mice (6). In contrast, we observed lower-
C57BL/6 mice showed modest responses to anti-TNF-α therapy, and corticosteroid treatment with clobetasol produced variable results. However, in some endpoints, anti-TNF-α even exacerbated inflammatory markers, including increases in IFN-γ levels in plasma. Separate studies have demonstrated that anti-IL-12/23p40 therapy also has efficacy in this strain.
BALB/c Mice: Higher Disease Severity and Increased Cytokine Response
BALB/c mice also developed robust psoriasis-like disease following IMQ treatment, with greater overall severity than C57BL/6 mice. Higher PASI scores during the study and
The stronger inflammatory profile in BALB/c mice was reflected by increased IL-17A expression, a key cytokine involved in human psoriasis pathogenesis. Cytokine levels typically peaked around Day 5, later than the peak seen in C57BL/6 mice. Immune profiling identified γδ T cells as primary drivers of inflammation, consistent across both strains. Systemic and local cytokine trends also mirrored each other, with IL-4 again showing delayed expression in skin relative to plasma.
BALB/c mice demonstrated a slightly more favorable response to anti-inflammatory therapies. Clobetasol significantly reduced disease severity across multiple parameters. Anti-TNF-α therapies showed only mild effects.
Choosing the Right Strain for Your Study
These findings highlight the importance of selecting the right strain to align with your compound’s mechanism of action. BALB/c mice may be the preferred choice for evaluating therapies that target inflammatory cytokine pathways or for studies where robust anti-inflammatory effects are expected. In contrast, C57BL/6 mice, which remain the strain of choice for comparison to transgenic or diet-induced obese mice, may offer advantages for therapies focused on remission. The study also demonstrated that positive controls, such as corticosteroids or biologics, can behave differently between strains—reinforcing the need for strain-specific study design to ensure reliable interpretation of treatment effects. By leveraging strain-specific differences in immune responses and treatment outcomes, researchers can improve study sensitivity, generate more meaningful data, and increase confidence in translational relevance.
Partner with Inotiv for Confident Study Design
At Inotiv, we are committed to providing flexible, scientifically rigorous preclinical models that help advance drug candidates toward clinical success. With a robust IMQ platform, tailored study designs, and deep expertise in immune pathway analysis, we help clients move forward with confidence, backed by solid science and expert support.
Contact us to discuss the full study results and how we can support your drug development program.
References
1. van der Fits, L. et al. (2009) J. Immunol. 182:5836.
2. Cai, Y. et al. (2011) Immunity 35:596.
3. Pantelyushin, S. et al. (2012) J. Clin. Invest. 122:2252.
4. Van Belle, A.B. et al. (2012) J. Immunol. 188:462.
5. Moos, S. et al. (2019) J. Invest. Dermatol. 139:1110.
6. Swindell, W.R. et al. (2017) Genome Med. 9:24.
7. Li, Q. et al. (2021) BMC Immunol. 22:11.