Titre :

Antibody-mediated neutralization of galectin-3 as a strategy for the treatment of systemic sclerosis.

Auteur(s) :

Ortega-Ferreira, Céline [Auteur]
Soret, Perrine [Auteur]
Robin, Gautier [Auteur]
Speca, Silvia [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Hubert, Sandra [Auteur]
Le Gall, Marianne [Auteur]
Desvaux, Emiko [Auteur]
Jendoubi, Manel [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Saint-Paul, Julie [Auteur]
Chadli, Loubna [Auteur]
Chomel, Agnès [Auteur]
Berger, Sylvie [Auteur]
Nony, Emmanuel [Auteur]
Neau, Béatrice [Auteur]
Fould, Benjamin [Auteur]
Licznar, Anne [Auteur]
Levasseur, Franck [Auteur]
Guerrier, Thomas [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Elouej, Sahar [Auteur]
Courtade-Gaïani, Sophie [Auteur]
Provost, Nicolas [Auteur]
Nguyen, The Quyen [Auteur]
Verdier, Julien [Auteur]
Launay, David [Auteur]
Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France [CeRAINO]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
De Ceuninck, Frédéric [Auteur]

Titre de la revue :

Nature Communications

Nom court de la revue :

Nat Commun

Numéro :

14

Pagination :

5291

Date de publication :

2023-09-02

ISSN :

2041-1723

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Systemic sclerosis (SSc) is an autoimmune, inflammatory and fibrotic disease with limited treatment options. Developing new therapies is therefore crucial to address patient needs. To this end, we focused on galectin-3 ...
Lire la suite >Systemic sclerosis (SSc) is an autoimmune, inflammatory and fibrotic disease with limited treatment options. Developing new therapies is therefore crucial to address patient needs. To this end, we focused on galectin-3 (Gal-3), a lectin known to be associated with several pathological processes seen in SSc. Using RNA sequencing of whole-blood samples in a cross-sectional cohort of 249 patients with SSc, Gal-3 and its interactants defined a strong transcriptomic fingerprint associated with disease severity, pulmonary and cardiac malfunctions, neutrophilia and lymphopenia. We developed new Gal-3 neutralizing monoclonal antibodies (mAb), which were then evaluated in a mouse model of hypochlorous acid (HOCl)-induced SSc. We show that two of these antibodies, D11 and E07, reduced pathological skin thickening, lung and skin collagen deposition, pulmonary macrophage content, and plasma interleukin-5 and -6 levels. Moreover, E07 changed the transcriptional profiles of HOCl-treated mice, resulting in a gene expression pattern that resembled that of control mice. Similarly, pathological pathways engaged in patients with SSc were counteracted by E07 in mice. Collectively, these findings demonstrate the translational potential of Gal-3 blockade as a therapeutic option for SSc.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Date de dépôt :

2024-01-11T22:16:57Z
2024-03-25T16:02:11Z