Immune-Endocrine Cross-Talk in Diabetes

Immunology Metabolism and endocrinology

Leader(s)

Sylvaine YOU Permanent researcher Directrice de recherche

The general objective of the Team is to better understand the multiple layers of cross-talk that take place between immune cells and pancreatic endocrine cells, contributing to tissue development, function and homeostasis or, in contrast, to pathological manifestations, in particular type 1 diabetes (T1D). Our project is composed of 3 major research axes: 1. Pancreatic endocrine cell function and biomarkers; 2. Immune mechanisms and biomarkers of T1D progression; 3. Development of novel immune modulatory and beta-cell protective therapeutics.

Using state-of-the-art and high throughput technologies (immunopeptidomics, proteomics, single cell/bulk RNAseq, multiparametric flow cytometry, imaging), sophisticated in vitro systems and animal models developed by the Team, our research program integrates fundamental and translational research, mouse and human studies, to decipher biological mechanisms in physiological and pathological contexts, which may lead to innovative therapeutic opportunities. The identification of novel beta-cell/T-cell biomarkers and druggable targets for T1D diagnosis, prognosis or treatment will promote clinical translation, valorization and international partnerships and recognition. It further synergizes with the activities of our satellite lab in Indianapolis (Indiana Bioscience Research Institute), which offers access to a state-of-the-art iPS platform to generate and genetically manipulate by CRISPR/Cas9 iPS-derived islet cells and to expertise in drug development against selected targets. In this perspective, we have already launched several clinical studies to screen for T1D risk in affected families. For more information, see our websites: www.dearlab.org ; www.humanbetacelllines.com

Team members

Carmen CAPITO Permanent researcher PH

Danièle DUBOIS Permanent researcher

Etienne LARGER Permanent researcher PU-PH

Roberto MALLONE Permanent researcher

Latif RACHDI Permanent researcher Chargé de recherche

Raphael SCHARFMANN Permanent researcher Research director

Sylvaine YOU Permanent researcher Directrice de recherche

Farah KOBAISI Contract researcher

François MIFSUD Contract researcher

Masaya OSHIMA Contract researcher

Fatoumata SAMASSA Contract researcher

Grégoire STYM-POPPER Contract researcher

Federica VECCHIO Contract researcher

Orlando BURGOS MORALES PhD student

Alexis FOUQUE PhD student

Clémentine HALLIEZ PhD student

Abir KOBAISI PhD student

Tin Hinan LASSOUANI PhD student

Widad NEFIDA PhD student

Christian AMUBIOYA Contract ITA Engineer

Barbara BRANDAO Contract ITA Engineer

Aliocha LO GIUDICE Contract ITA Engineer

Océane MAYEUR Contract ITA Engineer

Nina MODE Contract ITA Engineer

Margot PETIT Contract ITA Engineer

Ek-Tchay POV Contract ITA Engineer

Kethia SADALA ALANGI Contract ITA

Delphine THIBAUT Contract ITA Engineer

Anastasiia NIKOLAEVA Master

Cécile XU Master

Projects

Raphael SCHARFMANN

Pancreatic endocrine cell function and biomarkers (R. Scharfmann)

Metabolism and endocrinology

Sylvaine YOU
Roberto MALLONE

Immune mechanisms and biomarkers of T1D progression (S. You/R. Mallone)

Immunology

Sylvaine YOU
Roberto MALLONE

Development of novel immune modulatory and beta-cell protective therapeutics (S. You/R. Mallone/R. Scharfmann)

Immunology

Metabolism and endocrinology

Main publications and patents

PUBLICATIONS

A. Carré, F. Samassa, Z. Zhou, J. Perez-Hernandez, C. Lekka, A. Manganaro, M. Oshima, H. Liao, R. Parker, A. Nicastri, B. Brandao, M.L. Colli, D.L. Eizirik, J. Aluri, D. Patel, M. Göransson, O. Burgos Morales, A. Anderson, L. Landry, F. Kobaisi, R. Scharfmann, L. Marselli, P. Marchetti, S. You, M. Nakayama, S.R. Hadrup, S.C. Kent, S.J. Richardson, N. Ternette, R. Mallone. Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells. Nat Commun. 2025. 16, 765. doi.org/10.1038/s41467-025-55908-9.

Villalba A, Gitton Y, Aiello V, Toupin M, Mazaud-Guittot S, Chédotal A, Scharfmann R. Imaging human pancreatic endocrinogenesis during early prenatal life. Diabetes. 2024, Nov 27:db240641. doi: 10.2337/db24-0641.

Vecchio F, Carré A, Korenkov D, Zhou Z, Apaolaza P, Tuomela S, Burgos-Morales O, Snowhite I, Perez-Hernandez J, Brandao B, Afonso G, Halliez C, Kaddis J, Kent SC, Nakayama M, Richardson SJ, Vinh J, Verdier Y, Laiho J, Scharfmann R, Solimena M, Marinicova Z, Bismuth E, Lucidarme N, Sanchez J, Bustamante C, Gomez P, Buus S, the nPOD-Virus Working Group, You S, Pugliese A, Hyoty H, Rodriguez-Calvo T, Flodstrom-Tullberg M, Mallone R. Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses. Sci Adv. 2024, 10(10): eadl1122. Doi: 10.1126/sciadv.adl1122.

Carré A, Vecchio F, Flodstrom-Tullberg M, You S, Mallone R. Coxsackievirus and type 1 diabetes: diabetogenic mechanisms and implications for prevention. Endocr Reviews. 2023, 44(4): 737-751. doi.org/10.1210/endrev/bnad007

Rachdi L, Zhou Z, Berthault C, Lourenço C, Fouque A, Domet T, Armanet M, You S, Peakman M, Mallone R, Scharfmann R. Tryptophan metabolism promotes immune evasion in human pancreatic β cells. EBioMedicine. 2023, Sep;95:104740. doi: 10.1016/j.ebiom.2023.104740.

Corcos N, Culina S, Deligne C, Lavaud C, You S* and Mallone R*. Oral Fc-coupled preproinsulin achieves systemic and thymic delivery through the neonatal Fc receptor and partially delays autoimmune diabetes. Front Immunol. 2021, 12:616215. doi: 10.3389/fimmu.2021.616215.

Gonzalez-Duque S, Azoury ME, Colli ML, Afonso G, Turatsinze JV, Nigi L, Lalanne AI, Sebastiani G, Carré A, Pinto S, Culina S, Corcos N, Bugliani M, Marchetti P, Armanet M, Diedisheim M, Kyewski B, Steinmetz LM, Buus S, You S, Dubois-Laforgue D, Larger E, Beressi JP, Bruno G, Dotta F, Scharfmann R, Eizirik DL, Verdier Y, Vinh J, Mallone R. Conventional and neo-antigenic peptides presented by β cells are targeted by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. Cell Metab. 2018, 28(6):946-960.e6

Oshima M, Knoch KP, Diedisheim M, Petzold A, Cattan P, Bugliani M, Marchetti P, Choudhary P, Huang GC, Bornstein SR, Solimena M, Albagli-Curiel O, Scharfmann R. Virus-like infection induces human β cell dedifferentiation. JCI Insight. 2018, 3(3):e97732. doi: 10.1172/jci.insight.97732.

BREVETS

2022- EB19114 - patent under consideration on “biomarkers of autoimmune T cells for the diagnosis and treatment of type 1 diabetes”, by Inserm-Transfert; inventors R. Mallone, S. You, F. Samassa, M. Giraud.

2019 - WO/2019/175380 “Antigenic peptides deriving from Secretogranin V and uses thereof for the diagnosis and treatment of type 1 diabetes” filed by Inserm-Transfert on March 16 2018 (EP18305286); inventors R. Mallone, J. Vinh, D. Eizirik, M. Colli, G. Afonso, S. Gonzalez-Duque, Y. Verdier.

2019 - WO/2019/175381 “Antigenic peptides deriving from PCSK2 and uses thereof for the diagnosis and treatment of type 1 diabetes” filed by Inserm-Transfert on March 16 2018 (EP18305287); inventors R. Mallone, J. Vinh, G. Afonso, S. Gonzalez-Duque, Y. Verdier, M.E. Azoury.

2019 - WO/2019/175384 “Antigenic peptides deriving from Urocortin 3 and uses thereof for the diagnosis and treatment of type 1 diabetes” filed by Inserm-Transfert on March 16 2018 (EP18305288); inventors R. Mallone, J. Vinh, G. Afonso, S. Gonzalez-Duque, Y. Verdier, M.E. Azoury.

The Scharfmann group files many patents related to the generation of human beta cell lines (WO/2008/102000; WO/2003/033685; WO2013057164). They were the basis to create in 2005, a biotech company as a spin off from the lab. This company, EndoCells, is now named Human Cell Design (https://www.humancelldesign.com/) and is considered as a success story. RS is consultant for Human Cell Design. RS is also consultant for the french company ADOCIA (https://www.adocia.com/fr/) on their project related to islet encapsulation.