Use this URL to cite or link to this record in EThOS: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730431 |
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Title: | The role of CD1a and phospholipase A2 in psoriasis | ||||||
Author: | Cheung, Ka Lun |
ISNI:
0000 0004 6497 0575
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Awarding Body: | University of Oxford | ||||||
Current Institution: | University of Oxford | ||||||
Date of Award: | 2016 | ||||||
Availability of Full Text: |
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Abstract: | |||||||
Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 (Th17) response, yet it has proved challenging to identify relevant peptide-based T cell antigens. Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. Here we observed expression of a cytosolic PLA2 (PLA2G4D) in mast cells in psoriatic lesions but not in healthy skin, but unexpectedly also found the PLA2G4D activity to be extracellular. This could be explained by IFN-α-induced mast cell release of exosomes, which transferred cytosolic PLA2 activity to neighbouring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid specific CD1a-reactive T cells inducing production of IL-22 and IL-17. Circulating and skin-resident T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared to healthy controls. Overall these data present an alternative model of psoriasis pathogenesis in which unconventional lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA2 inhibition may have therapeutic potential for psoriasis.
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Supervisor: | Ogg, Graham | Sponsor: | Not available | ||||
Qualification Name: | Thesis (Ph.D.) | Qualification Level: | Doctoral | ||||
EThOS ID: | uk.bl.ethos.730431 | DOI: | Not available | ||||
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