| Autor: |
Hardman, CS, Chen, Y-L, Wegrecki, M, Ng, SW, Murren, R, Mangat, D, Silva, J-P, Munro, R, Chan, WY, O'Dowd, V, Doyle, C, Mori, P, Popplewell, A, Rossjohn, J, Lightwood, D, Ogg, GS |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Nature Communications. 13 |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-022-35071-1 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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