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

Roberto Lande; Elisabetta Botti; Camilla Jandus; Danijel Dojcinovic; Giorgia Fanelli; Curdin Conrad; Georgios Chamilos; Laurence Feldmeyer; Barbara Marinari; Susan Chon; Luis Vence; Valeria Riccieri; Phillippe Guillaume; Alex A. Navarini; Pedro Romero; Antonio Costanzo; Enza Piccolella; Michel Gilliet; Loredana Frasca

doi:10.1038/ncomms6621

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

Roberto Lande, Elisabetta Botti, Camilla Jandus, Danijel Dojcinovic, Giorgia Fanelli, Curdin Conrad, Georgios Chamilos, Laurence Feldmeyer, Barbara Marinari, Susan Chon, Luis Vence, Valeria Riccieri, Phillippe Guillaume, Alex A. Navarini, Pedro Romero, Antonio Costanzo, Enza Piccolella, Michel Gilliet, Loredana Frasca

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396 Scopus citations

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-3, 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.

Original language	English (US)
Article number	5621
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6621
State	Published - Dec 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Lande, R., Botti, E., Jandus, C., Dojcinovic, D., Fanelli, G., Conrad, C., Chamilos, G., Feldmeyer, L., Marinari, B., Chon, S., Vence, L., Riccieri, V., Guillaume, P., Navarini, A. A., Romero, P., Costanzo, A., Piccolella, E., Gilliet, M., & Frasca, L. (2014). The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nature communications, 5, Article 5621. https://doi.org/10.1038/ncomms6621

Lande, R, Botti, E, Jandus, C, Dojcinovic, D, Fanelli, G, Conrad, C, Chamilos, G, Feldmeyer, L, Marinari, B, Chon, S, Vence, L, Riccieri, V, Guillaume, P, Navarini, AA, Romero, P, Costanzo, A, Piccolella, E, Gilliet, M & Frasca, L 2014, 'The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis', Nature communications, vol. 5, 5621. https://doi.org/10.1038/ncomms6621

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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-3, 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.",

author = "Roberto Lande and Elisabetta Botti and Camilla Jandus and Danijel Dojcinovic and Giorgia Fanelli and Curdin Conrad and Georgios Chamilos and Laurence Feldmeyer and Barbara Marinari and Susan Chon and Luis Vence and Valeria Riccieri and Phillippe Guillaume and Navarini, {Alex A.} and Pedro Romero and Antonio Costanzo and Enza Piccolella and Michel Gilliet and Loredana Frasca",

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AU - Lande, Roberto

AU - Botti, Elisabetta

AU - Jandus, Camilla

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AU - Conrad, Curdin

AU - Chamilos, Georgios

AU - Feldmeyer, Laurence

AU - Marinari, Barbara

AU - Chon, Susan

AU - Vence, Luis

AU - Riccieri, Valeria

AU - Guillaume, Phillippe

AU - Navarini, Alex A.

AU - Romero, Pedro

AU - Costanzo, Antonio

AU - Piccolella, Enza

AU - Gilliet, Michel

AU - Frasca, Loredana

PY - 2014/12

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N2 - 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-3, 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.

AB - 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-3, 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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The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis

Abstract

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