Immunology of diabetes

Metabolism and endocrinology Immunology

Leader(s)

Agnès LEHUEN Permanent researcher Responsable d'équipe

Taking advantage of our expertise on mouse models and interactions with several clinical departments, our research focuses on the role of adaptive and innate immune cells in type 1 (T1D) and type 2 (T2D) diabetes/obesity and genetics of diabetes. Our projects serve to understand disease mechanisms, discover biomarkers and develop therapeutic strategies.

The specific objectives are:
- Determine the role of innate T lymphocytes in the regulation of T1D. NKT and MAIT cells are unconventional T cells that act as sensors of metabolic abnormalities. These innate-like T cells can regulate both innate and adaptive immunity. Our data demonstrated the efficiency of NKT and MAIT cells in preventing T1D.
- Determine the role of innate T lymphocytes in the regulation of T2D, obesity and non-alcoholic fatty liver disease. We have shown that in patients and mouse models, T2D and obesity induce alterations in MAIT cells, and high levels of inflammatory cytokines in adipose tissue. With our collaborators, we have shown that MAIT cells are profibrogenic in the liver of cirrhotic patients associated with non-alcoholic steatohepatitis (NASH).
- Develop "humanized" murine models that more closely mimic human T1D and understand the role of co-stimulation pathways in autoimmune activation against a given self-tissue. Such models are crucial for the initiation of clinical trials exploring vaccination strategies with cell antigens aimed at restoring immune tolerance.
- Identify genetic factors involved in the diversity of juvenile-onset diabetes, ranging from multifactorial T1D to monogenic forms of diabetes whose clinical presentation may be atypical or not.

Members

Jacques BELTRAND Permanent researcher

Christian BOITARD Permanent researcher

Cécile JULIER Permanent researcher

Agnès LEHUEN Permanent researcher Responsable d'équipe

Ute ROGNER Permanent researcher Directeur de recherche

Amine TOUBAL Permanent researcher Chargé de recherche

François LEMONNIER Emeritus status

Lucie DESMAREST-BEAUDOIN Permanent ITA Ingénieure d'étude

Anne PHILIPPI Permanent ITA Ingénieur de recherche

Valérie SENÉE Permanent ITA Ingénieure d'étude

Léo BERTRAND Contract researcher Post-doctorant

Adrien CAFFIERS PhD student

Jeanne NAVARRE PhD student

Kevin PERGE PhD student

Gaëlle VERMILLAC PhD student

Anne DEGAVRE Contract ITA Ingénieur de recherche

Camille PERON Contract ITA Ingénieur d'étude

Amandine AIT OUFELLA Master

Ellyne DURAND-PATTI Master

Sophie PELET Master

Projects

Image vignette projet Le rôle des lymphocytes T de type inné dans la régulation du DT1

Agnès LEHUEN
Jacques BELTRAND

The role of innate-like T cells in the regulation of T1D

Immunology

Metabolism and endocrinology

Vignette projet Le rôle des lymphocytes T innés dans l'obésité, le diabète de type 2 et stéatose hépatique non alcoolique

Ute ROGNER
Amine TOUBAL

The role of innate T cells in obesity, type 2 diabetes and non-alcoholic fatty liver disease.

Metabolism and endocrinology

Immunology

Cécile JULIER

Genetics of diabetes

Cellular plasticity and reproduction

Metabolism and endocrinology

Vignette projet Modèles de souris « humanisées »

Christian BOITARD

'Humanized’ mouse models

Immunology

Publications

Search for a publication

Publication year

Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.

2021 - PMID: 33531712

Héloïse Flament et al.

Nature immunology

Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity.

2020 - PMID: 32709874

Amine TOUBAL et al.

Nature communications

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes.

2017 - PMID: 28991267

Rouxel et al.

Nature immunology

Patents and networks

PATENTS

European patent “Methods and kits of assessing status, risk or prognosis of type 1 diabetes”
EP16 305 319.2 on March 22 2016
PCT/EP2017/056859 on March 22 2017 (WO2017/162759) via le site espacenet de l’OEB.
US2019011432 (A1) on 2019-01-10
Lehuen, J. Da Silva, I. Nel, L. Beaudoin

European patent « Methods and pharmaceutical compositions for the treatment of fibrosis with agents capable of inhibiting the activation of mucosal-associated invariant T (MAIT) cells »
EP2017/051669 on June 22 2017 (WO2018/234843) via le site espacenet de l’OEB.
US2021403573 (A1) on 2021-12-30
P. Hegde, E. Weiss, V. Paradis, A. Lehuen, S. Lotersztajn

European patent “USE OF AN AGENT CAPABLE OF INHIBITING THE ACTIVATION OF MAIT CELLS FOR THE TREATMENT OF OBESITY AND OBESITY-RELATED DISORDERS”
EP19 305 332.9 on March 19 2019
PCT/EP2020/057368 on March 18 2020 (WO2020/187955) via le site espacenet de l’OEB.
US2022184083 (A1) on 2022-06-16
A.Toubal, A. Lehuen

European patent «USE OF MAIT CELLS AS BIOMARKERS AND BIOTARGETS IN COVID-19» filled by Inserm-Transfert
EP20 305 983.7 on September 04 2020
PCT/EP2021/073742 on August 27 2021 (WO2022/043496) via le site espacenet de l’OEB.
H. Flament, M. Rouland, L. Beaudoin, A. Toubal, R.C. Monteiro, A. Lehuen

European patent «USE OF TNF-ALPHA BLOCKING AGENT FOR PREVENTING, SUPPRESSING AND/OR DELAYING THE ONSET OF TYPE 1 DIABETES»
EP21 305 178.2 on February 10 2021
PCT/EP2022/053148 on February 09 2022 (WO2022/171685) accessible online via le site de l’OMPI
M. Rouland, L. Beaudoin, L. Beltrand, A. Lehuen

CLINICAL VALORISATION

Interactions entre les cellules MAIT, la muqueuse et le microbiome intestinal au cours du développement du diabète de type 1 MAIT, DT1 et microbiome
Périmétre : Régional
Instance, agence publique : INSERM
Niveau d'implication : Coordinateur
Date du début : 01 février 2022

MAIT and SARS-CoV2 with COVID-19 REACTing, COVIDICUS, RADIPEM cohorts
Périmètre : Régional
Instance, agence publique : AP-HP, INSERM, Tours hospital
Niveau d'implication : Coordinateur
Date du début : 05 février 2020

Intitulé : RHU QUID NASH
Périmètre : Régional
Instance, agence publique : AP-HP et INSERM
Niveau d'implication : Partenaire
Date du début : 27 janvier 2018

MAJOR FINANCING

2021 - 2024 INSERM Programme Microbiote
2021 - 2025 ANR HepadiMAIT
2020 - 2025 ANR Labex Inflamex
2019 - 2024 Label "Equipe FRM"
2019 - 2024 Award of the Fondation Francophone pour la Recherche sur le Diabète
2019 - 2020 Award of the Juvenile Diabetes Research Foundation
2018 - 2021 ANR Diab1MAIT
2017 - Network Research Hospital-University in Health (RHU QUID NASH)

Funding

Contact

Agnès Lehuen

+33(0) 1 76 53 55 90

Contact by email

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Cellular factors involved in human immunodeficiency virus-1 (HIV-1) early infection steps: KAP1, p21, NLRP3 and SUGT1

Advances in the pathophysiology of myeloproliferative neoplasms and in their targeted treatments

Pluripotent stem cells in cell therapy and disease modeling in diabetes

Séminaire Trans-sciences : Diversité / unicité des planètes et du vivant

Mechanics of blastocyst morphogenesis