Titre :

Characteristics and impact of infiltration of B-cells from systemic sclerosis patients in a 3D healthy skin model.

Auteur(s) :

Le Maître, Mathilde [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Guerrier, Thomas [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Collet, Aurore [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Derhourhi, Mehdi [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Meneboo, Jean-Pascal [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Toussaint, Bénédicte [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Bonnefond, Amelie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Villenet, Celine [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Sebda, Shéhérazade [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Bongiovanni, Antonino [Auteur]
Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41
Tardivel, Myriem [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Simon, Myriam [Auteur]
Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France [CeRAINO]
Jendoubi, Manel [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Daunou, Blanche [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Largy, Alexis [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Figeac, Martin [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Dubucquoi, Sylvain [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Pôle de Biologie Pathologie Génétique [CHU Lille]
Launay, David [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Titre de la revue :

Frontiers in Immunology

Nom court de la revue :

Front Immunol

Numéro :

15

Pagination :

1373464

Date de publication :

2024-08-27

ISSN :

1664-3224

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Introduction: In systemic sclerosis (SSc), B-cells are activated and present in the skin and lung of patients where they can interact with fibroblasts. The precise impact and mechanisms of the interaction of B-cells and ...
Lire la suite >Introduction: In systemic sclerosis (SSc), B-cells are activated and present in the skin and lung of patients where they can interact with fibroblasts. The precise impact and mechanisms of the interaction of B-cells and fibroblasts at the tissular level are poorly studied. Objective: We investigated the impact and mechanisms of B-cell/fibroblast interactions in cocultures between B-cells from patients with SSc and 3-dimensional reconstituted healthy skin model including fibroblasts, keratinocytes and extracellular matrix. Methods: The quantification and description of the B-cell infiltration in 3D cocultures were performed using cells imagery strategy and cytometry. The effect of coculture on the transcriptome of B-cells and fibroblasts was studied with bulk and single-cell RNA sequencing approaches. The mechanisms of this interaction were studied by blocking key cytokines like IL-6 and TNF. Results: We showed a significant infiltration of B-cells in the 3D healthy skin model. The amount but not the depth of infiltration was higher with B-cells from SSc patients and with activated B-cells. B-cell infiltrates were mainly composed of naïve and memory cells, whose frequencies differed depending on B-cells origin and activation state: infiltrated B-cells from patients with SSc showed an activated profile and an overexpression of immunoglobulin genes compared to circulating B-cells before infiltration. Our study has shown for the first time that activated B-cells modified the transcriptomic profile of both healthy and SSc fibroblasts, toward a pro-inflammatory (TNF and IL-17 signaling) and interferon profile, with a key role of the TNF pathway. Conclusion: B-cells and 3D skin cocultures allowed the modelization of B-cells infiltration in tissues observed in SSc, uncovering an influence of the underlying disease and the activation state of B-cells. We showed a pro-inflammatory effect on skin fibroblasts and pro-activation effect on infiltrating B-cells during coculture. This reinforces the role of B-cells in SSc and provide potential targets for future therapeutic approach in this disease.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille
CNRS
Inserm
Institut Pasteur de Lille

Collections :

• Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41

Date de dépôt :

2024-08-28T21:06:26Z
2024-09-30T15:25:19Z