Using Ex Vivo Skin Explants to Study Local Immune Responses in Psoriasis and Atopic Dermatitis

Chronic inflammatory skin diseases such as psoriasis and atopic dermatitis (AD) are driven by complex immune responses that involve both resident skin cells and infiltrating immune populations. While in vitro models and animal systems have provided valuable insights, they often fail to fully capture the local immune dynamics within human skin. Ex vivo skin explants derived from diseased human donors offer a powerful alternative — one that preserves the architecture, immune milieu, and cytokine environment of living tissue.¹ 

Understanding the Complexity of Local Immune Responses 

In conditions like psoriasis and AD, inflammation is not solely mediated by circulating immune cells. The skin itself — particularly keratinocytes, fibroblasts, and resident immune populations — plays an active role in amplifying or regulating these responses. In psoriasis, for instance, activation of the IL-23/Th17 axis leads to elevated IL-17 and IL-22 signaling, driving keratinocyte hyperproliferation and sustained inflammation. In contrast, AD is dominated by a Th2-skewed response characterized by IL-4, IL-5, and IL-13, which disrupts the skin barrier and promotes itch and infection susceptibility. 

Recent research shows that psoriasis is driven by a dynamic interplay between innate and adaptive immune cells that form a self-sustaining inflammatory loop within the skin. It often begins when keratinocytes or dendritic cells detect environmental stress, such as infection or tissue injury, and release inflammatory cytokines including TNF-α and type I interferons. These early signals recruit and activate dendritic cells, which produce IL-23 — a key cytokine that promotes the expansion of IL-17-secreting T cells. These Th17 cells, together with other sources such as γδ T cells and innate lymphoid cells, release IL-17A, IL-17F, and IL-22, which act directly on keratinocytes to amplify inflammation and accelerate skin cell turnover. 

Keratinocytes are far from passive participants. Once activated, they produce antimicrobial peptides and proinflammatory mediators like IL-36 and S100 proteins, which in turn stimulate additional immune cell recruitment. The result is a feed-forward cycle between keratinocytes, T cells, and dendritic cells that sustains chronic inflammation even after external triggers have subsided. Neutrophils also infiltrate psoriatic lesions, releasing extracellular traps and proteases that further fuel tissue damage and immune activation. Meanwhile, some CD8⁺ T cells acquire tissue-resident memory phenotypes, allowing them to persist in the skin and potentially drive relapse after clinical remission. 

Genetic studies have revealed that key susceptibility loci, such as HLA-C*06:02, IL23R, and TNFAIP3, influence antigen presentation, cytokine signaling, and NF-κB regulation — pathways that converge on this IL-23/IL-17 inflammatory axis. The combined effect is a highly localized, self-reinforcing immune response that is uniquely suited to study in diseased human skin explants, where these cellular and molecular interactions remain intact.^{2, 3}

While psoriasis exemplifies a Th17/Th1-driven inflammatory condition, atopic dermatitis (AD) represents a distinct but equally complex immune environment dominated by Th2-biased responses. In AD, keratinocyte dysfunction and filaggrin deficiency compromise the epidermal barrier, allowing allergens and microbes to penetrate and activate Langerhans cells and dendritic cells. These cells produce thymic stromal lymphopoietin (TSLP), IL-25, and IL-33, which promote the activation of Th2 cells and innate lymphoid cells type 2 (ILC2s). The resulting IL-4, IL-5, and IL-13 signaling drives IgE production, eosinophil recruitment, and further barrier disruption. Chronic lesions often evolve to include Th1 and Th22 components, creating a shifting immune landscape that mirrors disease progression from acute to chronic stages. Studying AD in ex vivo diseased skin explants allows researchers to capture these temporal and spatial immune dynamics in a way that in vitro models cannot.  

Advantages of Using Diseased Human Skin Explants 

Unlike reconstructed skin or animal models, diseased explants retain the full complexity of human pathology, including immune cell infiltration, altered keratinocyte differentiation, and extracellular matrix remodeling. They preserve the cytokine environment characteristic of psoriasis or AD, where IL-17, IL-22, or IL-4 signaling actively shapes tissue behavior. This allows researchers to study therapeutic effects within a true disease context rather than a simulated one. 

By way of example, a recent study, demonstrated the culture of full-thickness punch biopsies from lesional psoriasis skin to create an ex vivo disease model that retained the complex immune and structural features of the original tissue.⁴ The explants maintained viability and characteristic psoriatic inflammation for up to 96 hours, including elevated IL-17 and IL-23 pathway activity. When treated with a corticosteroid or an anti-IL-17A antibody, the explants showed marked reductions in inflammatory mediators such as IL-8 and DEFB4, mirroring known clinical drug responses. This study demonstrated that diseased human skin explants not only preserve the local immune microenvironment but also offer a translationally relevant platform to evaluate therapeutic mechanisms and efficacy in a controlled, patient-specific context. 

Because the tissue architecture and resident immune cells remain intact, diseased explants enablein-depth examination of cytokine crosstalk, leukocyte recruitment, and barrier repair under near-physiological conditions. For example, IL-17-driven chemokine production by keratinocytes can be monitored directly, providing mechanistic insight into how candidate drugs influence inflammation at its source.⁵

These models also reflect patient-specific genetics and inflammatory variability, offering stronger translational predictivity than animal studies. When evaluating biologics or small-molecule inhibitors targeting pathways such as IL-23 or JAK-STAT, ex vivo diseased tissue can reveal human-relevant responses that align more closely with clinical outcomes. 

Bridging the Gap Between Bench and Bedside 

By combining patient-derived diseased tissue with advanced molecular analyses, ex vivo explant studies provide a unique bridge between cell-based assays and clinical trials. These models capture donor-to-donor variability — a critical factor in immune-mediated diseases — and can help predict patient responses more accurately than animal studies. 

As the demand for human-relevant, data-rich models continues to rise in dermatology research, diseased skin explants represent a crucial tool for understanding the localized immune responses that drive chronic inflammatory skin conditions. They not only deepen our understanding of disease pathophysiology but also accelerate the development of more effective, targeted therapies for patients living with psoriasis and atopic dermatitis. 

References: 

1. Ex Vivo Studies - Eurofins Scientific, www.eurofins.com/cosmetics/services/ex-vivo-studies/. Accessed 7 Nov. 2025.
2. Sieminska I, Pieniawska M, Grzywa TM. The Immunology of Psoriasis-Current Concepts in Pathogenesis. Clin Rev Allergy Immunol. 2024 Apr;66(2):164-191. doi: 10.1007/s12016-024-08991-7. Epub 2024 Apr 20. PMID: 38642273; PMCID: PMC11193704.
3. Li, L.; Lu, J.; Liu, J.; Wu, J.; Zhang, X.; Meng, Y.; Wu, X.; Tai, Z.; Zhu, Q.; Chen, Z. Immune cells in the epithelial immune microenvironment of psoriasis: Emerging therapeutic targets. Front. Immunol. 2024, 14, 1340677
4. Tiirikainen ML, Woetmann A, Norsgaard H, Santamaria-Babí LF, Lovato P. Ex vivo culture of lesional psoriasis skin for pharmacological testing. J Dermatol Sci. 2020 Feb;97(2):109-116. doi: 10.1016/j.jdermsci.2019.12.010. Epub 2019 Dec 27. PMID: 31948839.
5. Cheuk S, Martini E, Bergh K, Chang D, Rethi B, Ståhle M, Eidsmo L. Granzyme A potentiates chemokine production in IL-17-stimulated keratinocytes. Exp Dermatol. 2017 Sep;26(9):824-827. doi: 10.1111/exd.13284. Epub 2017 Apr 10. PMID: 28094457.