[HTML][HTML] The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis

R Lande, E Botti, C Jandus, D Dojcinovic… - Nature …, 2014 - nature.com
R Lande, E Botti, C Jandus, D Dojcinovic, G Fanelli, C Conrad, G Chamilos, L Feldmeyer
Nature communications, 2014nature.com
Psoriasis is a common T-cell-mediated skin disease with 2–3% prevalence worldwide.
Psoriasis is considered to be an autoimmune disease, but the precise nature of the
autoantigens triggering T-cell activation remains poorly understood. Here we find that two-
thirds of patients with moderate-to-severe plaque psoriasis harbour CD4+ and/or CD8+ T
cells specific for LL37, an antimicrobial peptide (AMP) overexpressed in psoriatic skin and
reported to trigger activation of innate immune cells. LL37-specific T cells produce IFN-γ …
Abstract
Psoriasis is a common T-cell-mediated skin disease with 2–3% prevalence worldwide. Psoriasis is considered to be an autoimmune disease, but the precise nature of the autoantigens triggering T-cell activation remains poorly understood. Here we find that two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4+ and/or CD8+ T cells specific for LL37, an antimicrobial peptide (AMP) overexpressed in psoriatic skin and reported to trigger activation of innate immune cells. LL37-specific T cells produce IFN-γ, and CD4+ T cells also produce Th17 cytokines. LL37-specific T cells can infiltrate lesional skin and may be tracked in patients blood by tetramers staining. Presence of circulating LL37-specific T cells correlates significantly with disease activity, suggesting a contribution to disease pathogenesis. Thus, we uncover a role of LL37 as a T-cell autoantigen in psoriasis and provide evidence for a role of AMPs in both innate and adaptive immune cell activation.
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