CD1a promotes systemic manifestations of skin inflammation

Hardman, Clare S., Chen, Yi-Ling, Wegrecki, Marcin, Ng, Soo Weei, Murren, Robert, Mangat, Davinderpreet, Silva, John-Paul, Munro, Rebecca, Chan, Win Yan, O’Dowd, Victoria, Doyle, Carl, Mori, Prashant, Popplewell, Andy, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Lightwood, Daniel and Ogg, Graham S. 2022. CD1a promotes systemic manifestations of skin inflammation. Nature Communications 13 , 7535. 10.1038/s41467-022-35071-1

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	8 December 2022
Date of Acceptance:	17 November 2022
Last Modified:	11 Oct 2023 19:40
URI:	https://orca.cardiff.ac.uk/id/eprint/154746

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