Psoriasis is a chronic inflammatory skin disease caused by an IL-23- and IL-17 driven immune response. Monocytes are regarded as key immune regulatory cells, which can be divided into three well-defined subsets: classical monocytes, intermediate monocytes, and non-classical monocytes (ncMo). The function of ncMo in skin inflammation remains largely unknown. Yet, our previous studies on slan+ (6-sulfo LacNAc) ncMo suggested that these cells contribute to human psoriasis skin inflammation. We here report on the role of ncMo in a model of psoriasis-like skin inflammation induced by imiquimod (IMQ). These studies were performed in wild type and mice lacking ncMo [Nr4a1 super enhancer knock-out mice (Nr4a1se_2 mice)]. With IMQ treatment, we observed a strong increase of ncMo numbers in the skin as well as their mobilization in blood. In Nr4a1se_2 mice lacking ncMo IMQ-induced psoriasis, IL-17 production of T cells and mRNA expression of IL-23p19, TNF-α as well as IL-1ß in skin was largely reduced. Interestingly, psoriasis skin inflammation was reinstalled when reconstituting Nr4a1se_2 mice with wild type ncMo prior to elicitating psoriasis. In search for defining how ncMo orchestrate IMQ-dependent skin inflammation, we observed that granulocyte recruitment to the skin required the presence of ncMo. This may be explained be the corresponding finding, that expression of the neutrophil recruiting chemokines CXCL1 and CXCL2 was only found in WT mice but not in mice devoid of ncMo. In summary, we discovered a critical role of ncMo for the recruitment of neutrophils, the development of an IL-17-dominated skin immune response and the clinical development of psoriasis like dermatitis induced by IMQ. These studies contribute to the understanding of the in vivo development of psoriasis skin lesions and identify ncMo as a new target cell for potential therapeutic intervention.

ESDR341 - Imiquimod-induced psoriasis requires non-classical monocytes

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.