Our research work focuses on Type 1 diabetes (T1D), an autoimmune disease resulting from the destruction of insulin-producing pancreatic beta 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 (1) fail to keep autoreactive T lymphocytes inoffensive and (2) make the beta cells more visible and vulnerable to the autoimmune attack. This research will allow us to identify novel therapeutic targets to prevent T1D. In this perspective, we have already launched several clinical studies to screen for T1D risk in affected families.
Main publications
1. D.L. Eizirik, F. Szymczak, R. Mallone. Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes? Nat Rev Endocrinol, doi: 10.1038/s41574-023-00826-3 (2023).
2. A. Sola-Gazagnes, C. Pecquet, S. Berré, P. Achenbach, L.A. Pierson, I. Virmoux-Buisson, J. M’Bemba, F. Elgrably, P. Moguelet, C. Boitard, S. Caillat-Zucman, M. Laanani, J. Coste, E. Larger, R. Mallone. Insulin allergy: a diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study. Diabetologia, 65:1278-1290 (2022).
3. M.E. Azoury*, M. Tarayrah*, G. Afonso, A. Pais, M.L. Colli, C. Maillard, C. Lavaud, L. Alexandre-Heymann, S. Gonzalez-Duque, Y. Verdier, J. Vinh, S. Pinto, S. Buus, D. Dubois-Laforgue, E. Larger, J.P. Beressi, G. Bruno, D.L. Eizirik, S. You, R. Mallone. Peptides derived from insulin granule proteins are targeted by CD8+ T cells across MHC Class I restrictions in humans and NOD mice. Diabetes, 69:2678-2690 (2020). Related Commentary: B.O. Roep. There is something about insulin granules. Diabetes, 69:2575-2577 (2020).
4. S. Gonzalez-Duque, M.E. Azoury, M.L. Colli, G. Afonso, J.V. Turatsinze, L. Nigi, A.I. Lalanne, G. Sebastiani, A. Carré, S. Pinto, S. Culina, N. Corcos, M. Bugliani, P. Marchetti, M. Armanet, M. Diedisheim, B. Kyewski, L.M. Steinmetz, S. Buus, S. You, D. Dubois-Laforgue, E. Larger, J.P. Beressi, G. Bruno, F. Dotta, R. Scharfmann, D.L. Eizirik, Y. Verdier, J. Vinh, R. Mallone. Conventional and neo-antigenic peptides presented by beta cells are preferentially targeted in the pancreas, but not in blood, of type 1 diabetic patients. Cell Metab, 28:946-960.e6 (2018).
5. S. Culina*, A.I. Lalanne*, G. Afonso, K. Cerosaletti, S. Pinto, G. Sebastiani, K. Kuranda, L. Nigi, A. Eugster, T. Østerbye, A. Maugein, J.E. McLaren, K. Ladell, E. Larger, J.P. Beressi, A. Lissina, V. Appay, H.W. Davidson, S. Buus, D.A. Price, M. Kuhn, E. Bonifacio, M. Battaglia, S. Caillat-Zucman, F. Dotta, R. Scharfmann, B. Kyewski, R. Mallone, the ImMaDiab Study Group. Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetes from healthy donors. Sci Immunol, 3:eaao4013 (2018). Cover Article and Related Commentary: M.R. Ehlers. Who let the dogs out? The ever-present threat of autoreactive T cells. Sci. Immunol., 3:eaar6602 (2018).
Keywords
Type 1 diabetes, autoimmunity, T cells, antigens, immune tolerance.