0000000000827708
AUTHOR
Christian Wohn
Aldara-Induced Psoriasis-Like Skin Inflammation: Isolation and Characterization of Cutaneous Dendritic Cells and Innate Lymphocytes
Psoriasis is a chronic auto-inflammatory skin disease of unknown etiology affecting millions of people worldwide. Dissecting the cellular networks and molecular signals promoting the development of psoriasis critically depends on appropriate animal models. Topical application of Aldara cream containing the Toll-like receptor (TLR)7-ligand Imiquimod induces skin inflammation and pathology in mice closely resembling plaque-type psoriasis in humans. The particular power of the Aldara model lies in examining the early events during psoriatic plaque formation, which is difficult to achieve in patients. Hence, recent reports using this model have challenged currently prevailing concepts concernin…
Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice.
Psoriasis is an autoinflammatory skin disease of unknown etiology. Topical application of Aldara cream containing the Toll-like receptor (TLR)7 agonist Imiquimod (IMQ) onto patients induces flares of psoriasis. Likewise, in mice IMQ triggers pathological changes closely resembling psoriatic plaque formation. Key cytokines like IL-23 and type-I IFN (IFN-I), both being produced mainly by dendritic cells (DCs), have been implicated in psoriasis. Although plasmacytoid DCs (pDCs) are the main source of IFNα and thought to initiate disease, conventional DCs (cDCs) appear to maintain the psoriatic lesions. Any role of cDCs during lesion formation remains elusive. Here, we report that selective ac…
Antagonization of IL-17A Attenuates Skin Inflammation and Vascular Dysfunction in Mouse Models of Psoriasis
Besides skin inflammation, patients with severe psoriasis suffer from an increased risk of cardiovascular mortality. IL-17A plays a central role in the development of psoriasis and might connect skin and vascular disease. The aim of this study was to clarify whether anti-IL-17A therapy could also ameliorate the vascular dysfunction associated with severe psoriasis. We analyzed three murine models with varying severities of psoriasis-like skin disease concerning their vascular function and inflammation: (i) K14-IL-17A(ind/+) mice with keratinocyte-specific IL-17A overexpression and an early-onset severe psoriasis-like phenotype; (ii) homozygous CD11c-IL-17A(ind/ind) and heterozygous CD11c-IL…