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A shift towards a type I immune response in chronic atopic dermatitis favours an IL-15 dependent tissue resident
Adewonuola A Alase1, Caroline Mann2, Antonia Kolb2
1University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.
Background:
Tissue resident memory (TRM) cells are of interest in chronic inflammatory skin diseases as they are believed to facilitate flares in the same anatomical area. IL-15 is an essential growth factor for the survival of TRM in the skin compartment. A main source of IL-15 are tissue-resident cells.
Objective:
The purpose of this study was to explore the role of IL-15 in the chronification process of atopic dermatitis (AD).
Methods:
Primary human keratinocytes and fibroblasts were cultured and exposed to a range of stimuli in order to assess their IL-15 expression and production, which were measured by qPCR and ELISA, respectively. RNAseq and PCR were performed from lesional and non-lesional atopic dermatitis (AD) biopsies.
Results:
We tested a range of type I and type II response-associated cytokines and PAMPs on primary human fibroblasts and keratinocytes. The main inducer for IL-15 in keratinocytes proved to be IFNγ, while fibroblasts showed responsiveness to long-term exposure to IL-4. Transcriptomic analyses of AD skin biopsies confirmed that IL-15 was associated with a higher IFN signature and longer disease duration, and a significant correlation was observed between IL-15 and the TRM molecules CCR8 and CD69.
Conclusion:
The epidermal compartment responds to IFNs with IL-15 expression. Analysis of patient-derived skin biopsies highlights higher expression of IL-15 in the context of a Th1 shift known to occur in chronic AD. These data suggest that flares require prompt intervention to avoid consolidation of an IFNγ-driven tissue memory.
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