Leader(s)
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Charles Nicolas
- 01 57 27 73 06
- nicolas.charles@inserm.fr
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Blank Ulrich
- 01 57 27 73 45
- ulrich.blank@inserm.fr
Laboratory of Immunopathology, Nephrology and Cell Signaling
Team Charles
Department Nephrology, Immunology and Hematology
Line-up
Researcher(s)
Research assistants
Post-doctoral fellows
Presentation
The LINCS project is focused on the pathophysiology of immune-related and chronic kidney diseases through translational approaches that involve in vitro and in vivo mechanistic studies as well as characterizations of patient cohorts. We aim to provide pathophysiology-based innovative diagnostic, prognostic and therapeutic tools to patients with chronic kidney diseases and immunopathologies.
The project is divided into three highly interconnected work packages (WP) capitalizing on our previously obtained scientific expertise, results and established strong clinical interface.
- WP1: Immunopathology
We established the contributions of basophils (Bφ) and autoreactive (AR) IgE to Lupus Nephritis (LN) pathogenesis. Our project aims at deciphering, inside secondary lymphoid organs (SLO), the Bφ functional relationships with surrounding cells and identify specific Bφ surface markers to develop innovative therapeutic strategies to ameliorate LN patient care. These approaches and mechanisms are as well developed in other Ab-mediated autoimmune diseases (AAID) where Bφ and AR IgE have a significant pathogenic role. The causal link between severe infectious diseases and the development of autoimmune diseases will be studied as well.
- WP2: Nephrology
WP2 investigates the pathophysiology of chronic kidney diseases (CKD) that lead to kidney fibrosis and loss of function. Concerning LN, we are identifying molecular and cellular factors involved in its extinction when patients undergo replacement therapy (hemodialysis). The aim is to develop novel therapeutic strategies to prevent end stage renal disease in SLE and other CKD. We aim at describing mast cell (MC) involvement in peritoneal fibrosis development that occurs in patients following peritoneal dialysis (PD) replacement therapies. The pathological mechanisms leading to accelerated kidney senescence in CKD will be addressed.
- WP3: Cell Signalling
We will pursue our studies on the intracellular trafficking and signalling pathways involved in degranulation and chemokine secretion by MC by conventional and unbiased approaches. Understanding the molecular mechanisms of inflammatory mediator release by MC will help developing intervention strategies that may allow to control the pro-inflammatory role of MC in allergic and kidney diseases and/or promote their regulatory functions.
Landmark publications
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Publication date : 22 April 2024 More
PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Nature Communications
Authors : Tchen John Simon Quentin Chapart Lea Thaminy Morgane Vibhushan Shamila Saveanu Loredana Lamri Yasmine Saidoune Fanny Lebourdais-Pacreau Emeline Pellefigues Christophe Bex-Coudrat Julie Hajime KARASUYAMA Kensuke MIYAKE Juan HIDALGO Padraic G. FALLON Papo Thomas Blank Ulrich Benhamou Marc Hanouna Guillaume Sacre Karim Daugas Eric Charles Nicolas
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Publication date : 09 August 2023 More
Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases
Allergy.
Authors : Charles Nicolas Inge Kortekaas-Krohn Emek Kocaturk Jörg Scheffel Sabine Altrichter Carolin Steinert Yi-Kui Xiang Jan Gutermuth Laurent L Reber Marcus Maurer
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Publication date : 11 January 2023 More
Pathogenic accumulation of T follicular helper cells in lupus disease depends on PD-L1 and IL-4 expressing basophils
medRxiv
Authors : Tchen John Simon Quentin Chapart Lea Lamri Yasmine Saidoune Fanny Lebourdais-Pacreau Emeline Pellefigues Christophe Bex-Coudrat Julie Karasuyama H Miyake K Hidalgo J Fallon PG Papo Thomas Blank Ulrich Benhamou Marc Hanouna Guillaume Sacre Karim Daugas Eric Charles Nicolas
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Publication date : 01 January 2023 More
Impact of BNT162b2 mRNA anti-SARS-CoV-2 vaccine on interferon-alpha production by plasmacytoid dendritic cells and autoreactive T cells in patients with systemic lupus erythematosus: The COVALUS project
J Autoimmun.
Authors : Mageau Arthur Tchen John Valentine Marie Ferré Pascale Nicaise-Roland Diane Descamps Nicole Delory Chrystelle François Celine Mendes Papo Thomas Tiphaine Goulenok Charles Nicolas Sacre Karim
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Publication date : 27 October 2022 More
Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation
Front Immunol.
Authors : Bratti Manuela Vibhushan Shamila Cyril Longé Koumantou Despoina Gaël Ménasché Benhamou Marc Nadine Varin-Blank Blank Ulrich Saveanu Loredana Ben Mkaddem Sanae
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Publication date : 01 October 2022 More
Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
Ann Rheum Dis.
Authors : Noemie Jourde-Chiche Nathalie Costedoat-Chalumeau Karine Baumstarck Anderson Loundou Laurence Bouillet Stéphane Burtey Valérie Caudwell Laurent Chiche Lionel Couzi Laurent Daniel Christophe Deligny Bertrand Dussol Stanislas Faguer Pierre Gobert Guillaume Gondran Antoine Huart Aurélie Hummel Emilie Kalbacher Adexandre Karra Marc Lambert Véronique Le Guern Ludivine Lebourg Sandrine Loubière Hélène Maillard-Lefebvre François Maurier Micheline Pha Viviane Queyrel Philippe Remy Françoise Sarrot-Reynauld David Verhelst Eric Hachulla Zahir Amoura Daugas Eric WIN-Lupus study group
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Publication date : 01 September 2022 More
Rab44 regulates murine mast cell-driven anaphylaxis through kinesin-1-dependent secretory granule translocation
J Allergy Clin Immunol.
Authors : Cyril Longé Bratti Manuela Mathieu Kurowska Vibhushan Shamila Pierre David Valère Desmeure Jian-Dong Huang Alain Fischer Geneviève de Saint Basile Fernando E Sepulveda Blank Ulrich Gaël Ménasché
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Publication date : 01 July 2022 More
Systemic lupus erythematosus flare following SARS-CoV2 infection: the implication of IFNα and anti-IFNα autoantibodies
Clin Exp Rheumatol.
Authors : Mageau Arthur Pascale Nicaise Roland Tiphaine Goulenok Carine Farkh Charles Nicolas Sacre Karim
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Publication date : 29 June 2022 More
CT-M8 Mice: A New Mouse Model Demonstrates That Basophils Have a Nonredundant Role in Lupus-Like Disease Development
Front Immunol.
Authors : Tchen John Simon Quentin Chapart Lea Pellefigues Christophe Hajime Karasuyama Kensuke Miyake Blank Ulrich Benhamou Marc Daugas Eric Charles Nicolas
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Publication date : 04 April 2022 More
AMG853, A Bispecific Prostaglandin D2 Receptor 1 and 2 Antagonist, Dampens Basophil Activation and Related Lupus-Like Nephritis Activity in Lyn-Deficient Mice
Front Immunol.
Authors : Pellefigues Christophe Tchen John Chaimae Saji Lamri Yasmine Charles Nicolas
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Publication date : 01 April 2022 More
Basophils and IgE in autoimmunity: Mechanisms and therapeutic targets
Med Sci (Paris).
Authors : Tchen John Charles Nicolas
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Publication date : 02 December 2021 More
CD62L on blood basophils: a first pre-treatment predictor of remission in severe lupus nephritis
Nephrol Dial Transplant.
Authors : Matthieu Halfon Delphine Bachelet Hanouna Guillaume Barbara Dema Pellefigues Christophe Pauline Manchon Cedric Laouenan Charles Nicolas Daugas Eric
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Publication date : 01 October 2021 More
The high affinity IgE receptor: a signaling update
Curr Opin Immunol.
Authors : Blank Ulrich Hua Huang Toshiaki Kawakami
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Publication date : 01 October 2021 More
Autoimmunity, IgE and FcεRI-bearing cells
Curr Opin Immunol.
Authors : Charles Nicolas
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Publication date : 01 August 2021 More
SARS-CoV-2 infection among inpatients with systemic lupus erythematosus in France: a nationwide epidemiological study
Ann Rheum Dis.
Authors : Mageau Arthur Geoffrey Aldebert Damien Van Gysel Papo Thomas Jean-François Timsit Sacre Karim
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Publication date : 01 April 2021 More
Basophils and IgE contribute to mixed connective tissue disease development
J Allergy Clin Immunol.
Authors : Lamri Yasmine Vibhushan Shamila Lebourdais-Pacreau Emeline Boedec Erwan Saidoune Fanny Arnaud Mailleux Bruno Crestani Blank Ulrich Benhamou Marc Papo Thomas Daugas Eric Sacre Karim Charles Nicolas
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Publication date : 01 February 2021 More
Effects of BAFF Neutralization on Atherosclerosis Associated With Systemic Lupus Erythematosus
Arthritis Rheumatol.
Authors : Saidoune Fanny Guillaume Even Lamri Yasmine Julie Chezel Anh-Thu Gaston Brigitte Escoubet Papo Thomas Charles Nicolas Antonino Nicoletti Sacre Karim
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Publication date : 30 December 2020 More
Mast Cell Chymase and Kidney Disease
International Journal of Molecular Sciences
Authors : Vibhushan Shamila Bratti Manuela Juan Eduardo Montero-Hernández Alaa El Ghoneimi Benhamou Marc Charles Nicolas Daugas Eric Blank Ulrich
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Publication date : 08 December 2020 More
IgE in the Pathogenesis of SLE: From Pathogenic Role to Therapeutic Target
Antibodies (Basel).
Authors : Lamri Yasmine Charles Nicolas
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Publication date : 01 March 2020 More
Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment
Kidney Int.
Authors : Lydia Celia Madjene Luca Danelli Albert Dahdah Vibhushan Shamila Bex-Coudrat Julie Lebourdais-Pacreau Emeline Celine Vaugier Julien Claver Loïc Rolas Maguelonne Pons Iris Karina Madera-Salcedo Walid Beghdadi El Ghoneimi Alaa Benhamou Marc Launay Pierre Magnus Abrink Gunnar Pejler Ivan Cruz Moura Charles Nicolas Daugas Eric Perianin Axel Blank Ulrich
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Publication date : 01 May 2019 More
Basophil involvement in lupus nephritis: a basis for innovation in daily care
Nephrol Dial Transplant.
Authors : Charles Nicolas Jonathan M Chemouny Daugas Eric
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Publication date : 20 November 2018 More
Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment
Front Immunol.
Authors : Ngo Nyekel Flavie Lebourdais-Pacreau Emeline Benadda Samira Msallam Rasha Åbrink Magnus Pejler Gunnar Davoust Jean Benhamou Marc Charles Nicolas Launay Pierre Blank Ulrich Gautier Gregory
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Publication date : 03 July 2018 More
Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation
Sci Signal.
Authors : Madera-Salcedo IK Danelli L Tiwari N Dema N Lebourdais-Pacreau Emeline Vibhushan Shamila Birnbaum J Agabriel C Liabeuf V Klingebiel C Menasche G Macias-Silva M Benhamou Marc Charles Nicolas González-Espinosa C Vitte J Blank Ulrich
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Publication date : 20 February 2018 More
Prostaglandin D2 amplifies lupus disease through basophil accumulation in lymphoid organs
Nat Commun.
Authors : Pellefigues Christophe Dema B Lamri Yasmine Saidoune Fanny Lohéac C Lebourdais-Pacreau Emeline Dussiot M Bidault C Marquet F Jablonski M Chemouny JM Jouan F Dossier A Chauveheid MP Gobert D Papo Thomas Karasuyama H Sacre Karim Daugas Eric Charles Nicolas
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Publication date : 11 August 2017 More
Basophils contribute to pristane-induced Lupus-like nephritis model
Sci Rep.
Authors : Barbara Dema Lamri Yasmine Pellefigues Christophe Lebourdais-Pacreau Emeline Saidoune Fanny Caroline Bidault Hajime Karasuyama Sacre Karim Daugas Eric Charles Nicolas
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Publication date : 15 March 2017 More
Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury
J Immunol.
Authors : Danelli L Madjene LC Madera-Salcedo I Gautier Gregory Lebourdais-Pacreau Emeline Ben Mkaddem Sanae Charles Nicolas Daugas Eric Launay Pierre Blank Ulrich
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Publication date : 10 March 2017 More
Phospholipid scramblase 1 amplifies anaphylactic reactions in vivo
PLoS One.
Authors : Kassas-Guediri A Bex-Coudrat Julie Lebourdais-Pacreau Emeline Launay Pierre Monteiro Renato Blank Ulrich Charles Nicolas Benhamou Marc