IL-23 Induces Atopic Dermatitis-Like Inflammation Instead of Psoriasis-Like Inflammation in CCR2-Deficient Mice

Abstract

Psoriasis is an immune-mediated chronic inflammatory skin disease, characterized by epidermal hyperplasia and infiltration of leukocytes into the dermis and epidermis. IL-23 is expressed in psoriatic skin, and IL-23 injected into the skin of mice produces IL-22-dependent dermal inflammation and acanthosis. The chemokine receptor CCR2 has been implicated in the pathogenesis of several inflammatory diseases, including psoriasis. CCR2-positive cells and the CCR2 ligand, CCL2 are abundant in psoriatic lesions. To examine the requirement of CCR2 in the development of IL-23-induced cutaneous inflammation, we injected the ears of wild-type (WT) and CCR2-deficient (CCR2−/−) mice with IL-23. CCR2−/− mice had increased ear swelling and epidermal thickening, which was correlated with increased cutaneous IL-4 levels and increased numbers of eosinophils within the skin. In addition, TSLP, a cytokine known to promote and amplify T helper cell type 2 (Th2) immune responses, was also increased within the inflamed skin of CCR2−/− mice. Our data suggest that increased levels of TSLP in CCR2−/− mice may contribute to the propensity of these mice to develop increased Th2-type immune responses.

Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

“…Thus, up-regulation of IL-20 may contribute to the proliferation of keratinocytes and development of a thickened epidermis (hyperkeratosis) and the scaly and crusted skin associated with advanced scabies. IL-23 is produced in excess in psoriatic skin [39]–[44]. In vivo , IL-23 is produced by keratinocytes and dendritic cells and its effect in skin pathology is mediated by Th17 cytokines [44].…”

Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

“…[23][24][25][26] Furthermore, the IL-23-injected mouse model, which has been traditionally considered to resemble psoriasis 27,28 and exhibits the largest (25%) transcriptomic homology with human psoriasis fingerprinting among existing ''psoriasis-like'' models, 29 has also been found to display T H 2 activation and simulate AD-like skin inflammation. 30 Although all murine AD-like models (with the exception of Flg-mutated mice) 16,[18][19][20]22,24,27 are visibly inflamed, it is difficult to macroscopically differentiate AD-like dermatitis in mice from lesions mimicking contact dermatitis (CD) or psoriasis. For example, because flaky tail mice exhibit T H 17-dominated skin inflammation, 31,32 this murine model might more closely simulate a psoriasis-like phenotype rather than AD-like fingerprinting.…”

New insights in the pathogenesis of atopic dermatitis

“…AD may depend on the presence or absence of specific cytokines (49). More recently, Bromley et al (50) showed that the chemokine (c-c motif) receptor 2-deficient mice which were injected intradermally with IL-23, a cytokine that increases the expression of IL-17 and IL-22 that characterize psoriatic lesions, developed skin lesions that resembled AD with elevated number of eosinophils and increased expression of IL-22, TSLP, and IL-4. The study did not find increased infiltration of Th2 cells in the lesions, suggesting that IL-22 may provide feedback to innate cells to increase allergic inflammation, rather than antimicrobial response, in chemokine (c-c motif) receptor 2-deficient mice.…”