T-cell Tolerance, Biomarkers and Therapies in type 1 diabetes

Immunology Metabolism and endocrinology

Leader(s)

Roberto MALLONE Permanent researcher Responsable d'équipe

Sylvaine YOU Permanent researcher Directrice de recherche

Our research work focuses on Type 1 diabetes (T1D), an autoimmune disease resulting from the destruction of insulin-producing pancreatic β cells by the immune system, in particular by autoreactive T lymphocytes. Interestingly, we all harbor these autoreactive T lymphocytes but they are in most cases “benign”. So why do they turn into a pathological and aggressive state in diabetic patients? To answer this question, we are exploring the mechanisms that (aim #1) fail to keep autoreactive T lymphocytes inoffensive and (aim #2) make the β cells more visible and vulnerable to the autoimmune attack. This research will allow us to identify novel therapeutic targets to prevent T1D (aim #3). In this perspective, we have already launched several clinical studies to screen for T1D risk in affected families.

For more information, see our website: www.dearlab.org

Team members

Danièle DUBOIS Permanent researcher

Roberto MALLONE Permanent researcher Responsable d'équipe

Sylvaine YOU Permanent researcher Directrice de recherche

François MIFSUD Contract researcher Post-doctorant

Fatoumata SAMASSA Contract researcher

Grégoire STYM-POPPER Contract researcher Post-doctorant

Orlando BURGOS MORALES PhD student

Clémentine HALLIEZ PhD student

Tin Hinan LASSOUANI PhD student

Widad NEFIDA PhD student

Federica VECCHIO PhD student

Christian AMUBIOYA Contract ITA Ingénieur d'étude

Barbara BRANDAO Contract ITA Ingénieure d'étude

Aliocha LO GIUDICE Contract ITA Ingénieur d'étude

Océane MAYEUR Contract ITA Ingénieure d'étude

Margot PETIT Contract ITA Ingénieur d'étude

Projects

Roberto MALLONE
Sylvaine YOU

Loss of immune ignorance

Sylvaine YOU
Roberto MALLONE

Loss of immune regulation

Immunology

Metabolism and endocrinology

Sylvaine YOU
Roberto MALLONE

Innovative therapies to restore “benign” autoimmunity

Immunology

Metabolism and endocrinology

5 main publications and patents

PUBLICATIONS

Carré A, Vecchio F, Flodstrom-Tullberg M, You S, Mallone R. Coxsackievirus and type 1 diabetes: diabetogenic mechanisms and implications for prevention. Endocrine Reviews, 2023, 44(4): 737-751. doi.org/10.1210/endrev/bnad007
Corcos N, Culina S, Deligne C, Lavaud C, You S*, Mallone R*. Oral Fc-Coupled Preproinsulin Achieves Systemic and Thymic Delivery Through the Neonatal Fc Receptor and Partially Delays Autoimmune Diabetes. Frontiers in immunology. 2021, 12, 616215. doi: 10.3389/fimmu.2021.616215.
Azoury ME, Tarayrah M, Afonso G, Pais A, Colli ML, Maillard C, Lavaud C, Alexandre-Heymann L, Gonzalez-Duque S, Verdier Y, Vinh J, Pinto S, Buus S, Dubois-Laforgue D, Larger E, Beressi JP, Bruno G, Eizirik DL, You S, Mallone R. Peptides Derived From Insulin Granule Proteins Are Targeted by CD8 + T Cells Across MHC Class I Restrictions in Humans and NOD Mice. Diabetes. 2020, 69:2678-2690. doi: 10.2337/db20-0013.
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 Metabolism. 2018, 28:946. doi:10.1016/j.cmet.2018.07.007.
Culina, S., Lalanne, A.I., Afonso, G., Cerosaletti, K., Pinto, S., Sebastiani, G., Kuranda, K., Nigi, L., Eugster, A., Østerbye, T., Maugein, A., McLaren, J.E., Ladell, K., Larger, E., Beressi, J.P., Lissina, A., Appay, V., Davidson, H.W., Buus, S., Price, D.A., Kuhn, M., Bonifacio, E., Battaglia, M., Caillat-Zucman, S., Dotta, F., Scharfmann, R., Kyewski, B., Mallone, R., the ImMaDiab Study Group (2018). Islet-reactive CD8 + T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Science immunology 3. 10.1126/sciimmunol.aao4013

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.