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• W4311784906 abstract "Inflammatory skin conditions are increasingly recognised as being associated with systemic inflammation. The mechanisms connecting the cutaneous and systemic disease are not well understood. CD1a is a virtually monomorphic major histocompatibility complex (MHC) class I-like molecule, highly expressed by skin and mucosal Langerhans cells, and presents lipid antigens to T-cells. Here we show an important role for CD1a in linking cutaneous and systemic inflammation in two experimental disease models. In human CD1a transgenic mice, the toll-like receptor (TLR)7 agonist imiquimod induces more pronounced splenomegaly, expansion of the peripheral blood and spleen T cell compartments, and enhanced neutrophil and eosinophil responses compared to the wild-type, accompanied by elevated skin and plasma cytokine levels, including IL-23, IL-1α, IL-1β, MCP-1 and IL-17A. Similar systemic escalation is shown in MC903-induced skin inflammation. The exacerbated inflammation could be counter-acted by CD1a-blocking antibodies, developed and screened in our laboratories. The beneficial effect is epitope dependent, and we further characterise the five best-performing antibodies for their capacity to modulate CD1a-expressing cells and ameliorate CD1a-dependent systemic inflammatory responses. In summary, we show that a therapeutically targetable CD1a-dependent pathway may play a role in the systemic spread of cutaneous inflammation." @default.
• W4311784906 created "2022-12-28" @default.
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• W4311784906 date "2022-12-07" @default.
• W4311784906 modified "2023-10-10" @default.
• W4311784906 title "CD1a promotes systemic manifestations of skin inflammation" @default.
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• W4311784906 doi "https://doi.org/10.1038/s41467-022-35071-1" @default.
• W4311784906 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36477177" @default.
• W4311784906 hasPublicationYear "2022" @default.

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