Search
O07 Filaggrin insufficiency renders keratinocyte-derived small extracellular vesicles capable of affecting CD1a-mediated T-cell responses and promoting allergic inflammation
Abstract
The association between FLG loss-of-function mutations and the development of atopic dermatitis (AD) indicates that filaggrin is critical to skin barrier function; the mutations are also linked to additional allergic manifestations, but it is unknown how the skin may influence inflammation in distant tissues. Here we investigated the impact of filaggrin insufficiency on keratinocyte-derived exosome-enriched small extracellular vesicles (sEVs) and found that those secreted by filaggrin-knockdown cells are extensively remodelled as a consequence of the abnormal keratinocyte differentiation process. The altered sEV lipidome changes the sEV capacity to promote T-cell responses by direct effect on self-lipid neoantigen generation, modulating the content of permissive (stimulatory) and nonpermissive (inhibitory) CD1a ligands released from the sEV membranes by phospholipase A2. Presentation of those lipids to T cells results in the redirection from a type 1 to a type 2 response. We found that the aberrant sEV lipid composition mirrors a generalized remodelling of cellular lipids resulting from dysregulated expression of multiple enzymes of lipid metabolic pathways, observed both in filaggrin knockdown keratinocytes in vitro and in the skin of patients with AD. Hence, filaggrin insufficiency background renders keratinocytes capable of supplying CD1a ligands which are capable of impeding both homeostasis-promoting and protective antimicrobial responses, enhancing type 2 T-cell activation to perpetuate inflammation in AD skin. sEV transfer by systemic circulation may promote similar effects in distant tissues.
Citations
-
0
CrossRef
-
0
Web of Science
-
0
Scopus
Authors (13)
-
Adrian Kobiela
-
Joanna Frackowiak
-
Natalia Kordulewska
-
Lilit Hovhannisyan
-
Aleksandra Bogucka
-
Rachel Etherington
-
Artur Pirog
-
Irena Dapic
-
Susanne Gabrielsson
-
Sara Brown
-
Graham Ogg
-
Danuta Gutowska-Owsiak
Cite as
Full text
full text is not available in portal
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
BRITISH JOURNAL OF DERMATOLOGY
no. 189,
pages e6 - e7,
ISSN: 0007-0963 - Language:
- English
- Publication year:
- 2023
- Bibliographic description:
- Kobiela A., Hewelt-Belka W., Frackowiak J., Kordulewska N., Hovhannisyan L., Bogucka A., Etherington R., Pirog A., Dapic I., Gabrielsson S., Brown S., Ogg G., Gutowska-Owsiak D.: O07 Filaggrin insufficiency renders keratinocyte-derived small extracellular vesicles capable of affecting CD1a-mediated T-cell responses and promoting allergic inflammation// BRITISH JOURNAL OF DERMATOLOGY -Vol. 189,iss. 1 (2023), s.e6-e7
- DOI:
- Digital Object Identifier (open in new tab) 10.1093/bjd/ljad174.007
- Sources of funding:
-
- Free publication
- Verified by:
- Gdańsk University of Technology
seen 65 times
Recommended for you
Keratinocyte-derived small extracellular vesicles supply antigens for CD1a-resticted T cells and promote their type 2 bias in the context of filaggrin insufficiency
- A. Kobiela,
- W. Hewelt-Belka,
- J. Frackowiak
- + 10 authors
Transcriptomic responses to wounding: meta-analysis of gene expression microarray data
- P. Sass,
- M. Dąbrowski,
- A. Charzyńska
- + 1 authors
Pathogenesis of psoriasis in the “omic” era. Part II. Genetic, genomic and epigenetic changes in psoriasis
- B. Nedoszytko,
- A. Szczerkowska-Dobosz,
- M. Stawczyk-Macieja
- + 22 authors
Direct injection liquid chromatography-mass spectrometry (DI-LC-MS) analysis for rapid lipidomic profiling of extracellular vesicles
- W. Hewelt-Belka,
- M. Młynarczyk,
- J. Matinha-Cardoso
- + 3 authors