The importance of immunity in the development of reliable animal models for psoriasis and atopic dermatitis

Abstract

Psoriasis (PS) and atopic dermatitis (AD) are common inflammatory skin diseases characterized by an imbalance in specific T‐cell subsets, resulting in a specific cytokine profile in patients. Obtaining models closely resembling both pathologies along with a relevant clinical impact is crucial for the development of new therapies because of the high prevalence of these diseases. Single‐gene mouse models developed until now do not fully reflect the complexity of these disorders, in part not only because of inherent differences between mice and humans but also because of the multifactorial nature of these pathologies. The skin‐humanized mouse model developed by our group, based on a tissue engineering approach, has been used to test therapeutic strategies, although this methodology is still technically challenging and not widely available. The skin‐humanized mouse models for PS and AD reproduce human skin phenotypes, providing valuable tools for drug development and testing in the preclinical setting. The tissue engineering approach allows the development of personalized medicine, covering the broad genotypic spectrum of these pathologies. This review highlights the main differences between available murine models focusing on the tissue‐specific immunity of PS and AD. We discuss their contribution to unravel the complex pathophysiology of these diseases and to translate this knowledge into more accurate therapies.

Vitamin D Receptor Gene Polymorphisms and Risk of Atopic Dermatitis in Chinese Han Population

“… 1 , 2 Innate and adaptive immunity have definitive roles in the development, maintenance and flare-up of AD. 3 , 4 Skin barrier dysfunctions of AD make the entry of antigens and pathogens into the skin possible. Once they come into skin, they would interact with dendritic cells, and then create a milieu that shapes the immune response to allergy reaction.…”

Translational Relevance of Mouse Models of Atopic Dermatitis

“…Looking to the future, newer techniques such as the bioengineered humanized skin model [17] and the transplantation of stimulated peripheral blood mononuclear cells (PBMC) [29] hold great promise in their potential ability reproduce population-specific immune signatures in mice. While these techniques are further explored and characterized, a more practical approach to improving existing models' translational relevance can be guided by efforts to increase their versatility by exploring modifications that selectively modulate inflammatory responses, such as the use of CMIT/MIT prior to OVA sensitization to bolster Th17 response [36], or by characterizing the inflammatory response demonstrated by different mouse strains to aid in the selection of a model that most closely mimics a desired immune signature [28,37].…”

“…While the contribution of IL-17-producing γδ T cells has been assessed in human psoriasis, their role in human AD remains uncharacterized [53,54]. Similarly, although humanized skin and PBMC models represent promising strategies to recreate specific inflammatory signatures in mice, xenografts are still subject to interference caused by interactions with host physiology [17].…”

Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

“…Transgenic mice are generated by expressing the transgene under the control of a basal keratinocyte keratin (K5/K14) promotor, resulting in a Th2 cytokine profile and dermal infiltration of macrophages, neutrophils, eosinophils, and mast cells [149]. Repeated challenges with haptens such as oxazolone (OXA), dinitrochlorobenzene (DNCB), and trinitrochlorobenzene (TNCB) also induced AD-like phenotypes [150,151]. More recently, AD mouse models induced by topical application of vitamin D3 and its synthetic analogue calcipotriol (MC903) have gained attention [148,152].…”