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ORIGINAL RESEARCH article

Front. Immunol.
Sec. B Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1373464
This article is part of the Research Topic B cells and the roles of B cell depleting therapies in autoimmune skin diseases: novel findings, challenges, and future perspective. View all 3 articles

Characteristics and impact of infiltration of B-cells from Systemic Sclerosis Patients in a 3D healthy skin model

Provisionally accepted
Mathilde Le Maître Mathilde Le Maître 1*Thomas Guerrier Thomas Guerrier 1Aurore Collet Aurore Collet 1,2Mehdi Derhourhi Mehdi Derhourhi 3,4Jean-Pascal Meneboo Jean-Pascal Meneboo 5Bénédicte Toussaint Bénédicte Toussaint 3,4Amélie Bonnefond Amélie Bonnefond 3,4,6Céline Villenet Céline Villenet 5Shéhérazade Sebda Shéhérazade Sebda 5Antonino Bongiovanni Antonino Bongiovanni 5Meryem Tardivel Meryem Tardivel 5Myriam Simon Myriam Simon 7Manel Jendoubi Manel Jendoubi 1Blanche Daunou Blanche Daunou 1Alexis Largy Alexis Largy 1Martin Figeac Martin Figeac 5Sylvain Dubucquoi Sylvain Dubucquoi 1,2David Launay David Launay 1,7
  • 1 U1286 Institute for Translational Research in Inflammation (INFINITE), Lille, France
  • 2 Pôle de Biologie Pathologie Génétique, Institut d'Immunologie, Centre Hospitalier Regional et Universitaire de Lille, Lille, Nord-Pas-de-Calais, France
  • 3 Université de Lille, Lille, Nord-Pas-de-Calais, France
  • 4 Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, Nord-Pas-de-Calais, France
  • 5 Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, Lille, France
  • 6 Department of Metabolism,Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, England, United Kingdom
  • 7 Service de Médecine Interne et d'Immunologie Clinique, Centre de Référence Des Maladies Auto-Immunes et Systémiques Rares du Nord et Nord-Ouest de France, Centre Hospitalier Regional et Universitaire de Lille, Lille, Nord-Pas-de-Calais, France

The final, formatted version of the article will be published soon.

    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.

    Keywords: B-cell, systemic sclerosis, Skin, 3D coculture, Fibrosis, fibroblast

    Received: 19 Jan 2024; Accepted: 23 Jul 2024.

    Copyright: © 2024 Le Maître, Guerrier, Collet, Derhourhi, Meneboo, Toussaint, Bonnefond, Villenet, Sebda, Bongiovanni, Tardivel, Simon, Jendoubi, Daunou, Largy, Figeac, Dubucquoi and Launay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mathilde Le Maître, U1286 Institute for Translational Research in Inflammation (INFINITE), Lille, France

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