Topical application of IMQ elicits an inflammatory reaction in murine skin characterized grossly by erythema and scaling. Histologically, the features include epidermal thickening, altered epidermal differentiation with retention of nuclei in stratum corneum, absence of epidermal granular layer and leukocyte infiltration in the dermis [31–33]. These features closely resemble human psoriasis so well that this regimen has been suggested as a fast and reproducible model of studying the condition [31, 43]. The effects of IMQ are mediated by TLR 7/8 which are mainly expressed by monocytes, macrophages and dendritic cells [31]. Studies have also suggested that IMQ also act on keratinocytes either through TLR 7 [44] or a TLR-independent mechanism [45].
The results of this study suggest that the skin of NMR shows neither TLR-mediated nor TLR-independent effects of IMQ. This finding is intriguing and affirms the uniqueness and possibly the exceptional nature of inflammatory/immune response of this animal. Recent findings have shown that innate immunity of NMR possesses a number of differences, in terms of cellular composition, from what is generally known in mammals [46]. It is therefore probable that the inflammatory/immuno-surveillance components/mechanisms in the NMR epidermis that would initiate IMQ-induced skin reactions are different from that of other mammals. NMR may either be possessing, within the epidermis, atypical Langerhans cells and/or plasmacytoid dendritic cells that lack the mechanisms that mediate IMQ responses. These cells are thought to form the first line of contact with IMQ via their TLR 7/8 thus mediating the effects [47, 48]. Future studies aiming at immunohistolocalization of Langerhans cells and TLR 7 in the NMR skin may clarify this. Although a clear explanation to the non-reaction of NMR skin to IMQ could not be adduced, our results affirm the exceptional and unique nature of NMR inflammation/immunity. Furthermore, inflammation has been established as a hallmark of cancer [49–51] and it is therefore likely that the unique inflammatory/immunosurveillance mechanism exhibited by this animal could also be a contributor to its resistance to cancer.
In studies using mice, IMQ was applied on shaven area over the dorsum of the animal. Shaving before application could be significant as it has been suggested to enhance percutaneous absorption of substances [52, 53]. Being hairless, neither shaving nor sham-shaving was performed before IMQ application in the NMR. This could therefore mean that in the study using NMR, IMQ was applied to a more intact barrier and therefore the access to the cells that mediate the IMQ effects was limited if not eliminated. Furthermore, the NMR is thought to have a thicker epidermis and stratum corneum [7]. It is also possible that in this animal, Langerhans cells are localized in the dermis rather than in epidermis. This makes the cells virtually inaccessible to the ligand (IMQ) for their TLR 7/8. Such an atypical distribution of epidermal cells to the dermis in this animal has been reported in regard to the melanocytes [7].
Reactive oxygen species (ROS) are reported to play a protective role against immune mediated diseases. Increasing ROS has been shown to attenuate IMQ-induced psoriatic dermatitis while administration of anti-oxidant, N-Acetylcysteine, aggravated the condition [54]. NMR has poor antioxidant capacity, a more pro-oxidative cellular environment and higher levels of oxidative damage to macromolecules as compared to age-matched mice [55–57]. It is possible that there are high ROS in the skin of NMR which in turn confers protection against IMQ-induced psoriasis-like inflammation. This hypothesis, however, needs to be backed by further studies to analyze antioxidant capacity, oxidative damage and pro-oxidative status of NMR skin.
in conclusion, topical application of IMQ does not induce psoriaform skin inflammation in the NMR. This could be due to a combination of various unique attributes of the animal’s skin structure and/or its inflammatory/immunosurveillance apparatus. The cells that interact with IMQ and mediate its effects may have atypical distribution such that access to IMQ is limited or they could also be lacking TLR 7/8 and other mechanisms that mediate IMQ effects. High ROS reported in NMR tissues could also be exhibited by the skin and thereby compounding its resistance or tolerance to IMQ. The animal could be a good negative model for studying psoriasis but as a prerequisite, further studies are necessary to characterize the mechanisms behind the non-reaction of the animal’s skin to IMQ.