Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus.

Détails

Ressource 1Demande d'une copie Sous embargo indéterminé.
Accès restreint UNIL
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_F216A4047EA8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus.
Périodique
International journal of molecular sciences
Auteur⸱e⸱s
Lande R., Pietraforte I., Mennella A., Palazzo R., Spinelli F.R., Giannakakis K., Spadaro F., Falchi M., Riccieri V., Stefanantoni K., Conrad C., Alessandri C., Conti F., Frasca L.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Statut éditorial
Publié
Date de publication
06/02/2021
Peer-reviewed
Oui
Volume
22
Numéro
4
Pages
1650
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to "self" nucleic acids, LL37 acts as "danger signal," leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while "fully-citrullinated" LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated "adjuvant-like" properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to "fully citrullinated-LL37," "fully carbamylated-LL37" maintains both innate and adaptive immune-cells' stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.
Mots-clé
LL37, post-translational modifications (PTM), systemic lupus erythematosus (SLE)
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/02/2021 14:30
Dernière modification de la notice
02/09/2022 6:39
Données d'usage