Institutes
Tissue and Systemic Immunity
The research of Tissue and Systemic Immunity focuses on unveiling the immunological mechanisms of insulin resistance in metabolically active tissues, both in obesity-associated type 2 diabetes (T2D) and in T1D.
To untangle diabetes heterogeneity and identify a distinct endotype featured by both autoimmunity and insulin resistance, the researchers of Tissue and Systemic Immunity group aim to determine:
- the relative weight of insulin resistance in the pathogenesis of autoimmune diabetes,
- if and how immune-mediated responses in metabolic tissues modulate insulin resistance,
- whether autoimmune mechanisms, and in particular autoreactive T lymphocytes, underlie insulin resistance.
Research activity
The lab's research line aims to elucidate how defective communication between immune cells and tissue parenchymal cells contributes to the pathogenesis of metabolic diseases in humans. By unraveling diabetes endotypes, this research lays the ground for the successful design and interpretation of clinical trials for the prevention and treatment of diabetes.
Tissue and Systemic Immunity research group benefits of a wide network of national and international collaborators, i.e. at the University of Siena (Italy), University of Campania “Luigi Vanvitelli” (Italy), UMC Utrecht (Netherlands), University of Canberra (Australia), Benaroya Research Institute (Seattle, WA, USA), University of Miami Miller School of Medicine (Miami, FL, USA), University of Pittsburgh (Pittsburgh, PA, USA). The research of Petrelli's lab is supported by the European Commission (Marie Skłodowska-Curie Action), AXA Research Fund, JDRF, Ministero della Salute (Giovani Ricercatori – Ricerca Finalizzata).
Garavelli S., Bruzzaniti S., Tagliabue E., Di Silvestre D., Prattichizzo F., Mozzillo E., Fattorusso V., La Sala L., Ceriello A., Puca A.A., Mauri P., Strollo R., Marigliano M., Maffeis C., Petrelli A., Bosi E., Franzese A., Galgani M., Matarese G., de Candia P. Plasma circulating miR-23~27~24 clusters correlate with the immunometabolic derangement and predict C-peptide loss in children with type 1 diabetes. Diabetologia 2020 (ahead of print)
Cardellini S., Socci C., Bissolati M., Pindozzi F., Giovenzana A., Saibene A., Bosi E., Battaglia M., Petrelli A. Enrichment of Tc1 cells and T cell resistance to suppression are associated with dysglycemia in the visceral fat of human obesity. BMJ Open Diabetes Research & Care 2020
Battaglia M., Ahmed S., Anderson M., Atkinson M.A., Becker D, Bingley P., Bosi E., Brusko T.M., Di Meglio L.A., Evans-Molina C., Gitelman S.E., Greenbaum C. J., Gottlieb P.A., Herold K.C., Hessner M.J., Knipp M.J., Jacobsen L., Krischer J.P., Long A.S., Lundgren M., McKinney E.F., Morgan N.G., Oram R.A., Pastinen T., Peters M.C., Petrelli A., Qian X., Redondo M.J., Roep B.O., Schatz D., Skibinski D., Peakman M., Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes Care, 2020 Jan;43(1):5-12
Vecchio F., Messina G., Giovenzana A., Petrelli A., New Evidence of Exocrine Pancreatopathy in Presymptomatic and Symptomatic Type 1 Diabetes. Curr Diab Rep. 2019 Aug 31;19(10):92.
Battaglia M, Petrelli A, Vecchio F., Neutrophils and type 1 diabetes: current knowledge and suggested future directions. Curr Opin Endocrinol Diabetes Obes. 2019 Aug;26(4):201-206
Petrelli A, Mijnheer G, Hoytema van Konijnenburg D, van der Wal MM, Giovannone B, Mocholi E, Vazirpanah N, Broen J.C., Hijnen D, Oldenburg B, Coffer P, Vastert SJ, Prakken BJ, Spierings E, Pandit A, Mokry M, van Wijk F. PD-1+ CD8 T cells are clonally-expanding effectors in human chronic inflammation. Journal of Clinical Investigation 2018 Oct 1;128(10):4669-4681.
Sebastiani G, Ventriglia G, Stabilini A, Socci C, Morsiani C, Laurenzi A, Nigi L, Formichi C, Mfarrej B, Petrelli A, Fousteri G, Brusko TM, Dotta F, Battaglia M. Regulatory T-cells from pancreatic lymphnodes of patients with type-1 diabetes express increased levels of microRNA miR-125a-5p that limits CCR2 expression. Scientific Reports 2017 Jul 31;7(1):6897
Petrelli A., BJ Prakken, N.D. Rosenblum, and EUtrain fellows. Developing Translational Medicine Professionals: the Marie Curie Actions Model. Journal of Translational Medicine, 2016 Nov 29;14(1):329.
Petrelli A. and F. van Wijk. CD8 T cells in human autoimmune arthritis: the unusual suspects. Nature Reviews Rheumatology, 2016 Jul;12(7):421-8
Petrelli A, Wehrens EJ, Scholman RC, Prakken BJ, Vastert SJ, van Wijk F. CD8+ T cell resistance to suppression at the site of autoimmune inflammation is self-sustained and can be reversed by TNF-α and IFN-γ blockade. Arthritis & Rheumatology, 2016 Jan;68(1):229-36.
Petrelli A, Tresoldi E, Mfarrej BJ, Paganelli A, Spotti D, Caldara R, Secchi A, Battaglia M. Generation of donor-specific T regulatory type 1 (Tr1) cells from patients on dialysis for cell therapy after kidney transplantation. Transplantation, 2015 Aug;99(8):1582-9.
Vergani A, Tezza S, D'Addio F, Fotino C, Liu K, Niewczas M, Bassi R, Molano RD, Kleffel S, Petrelli A, Soleti A, Ammirati E, Frigerio M, Visner G, Grassi F, Ferrero ME, Corradi D, Abdi R, Ricordi C, Sayegh MH, Pileggi A, Fiorina P. Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7. Circulation, 2013 Jan 29;127(4):463-75
Petrelli A, Di Fenza R, Carvello M, Gatti F, Secchi A and Fiorina P. Strategies to reverse Endothelial Progenitor Cell dysfunction in diabetes (review). Experimental Diabetes Research, 2012:471823.
Carvello M*, Petrelli A*, Vergani A, Lee KM, Tezza S, Chin M, Orsenigo E, Staudacher C, Secchi A, Dunussi-Joannopoulos K, Sayegh MH, Markmann JF and Fiorina P. Inotuzumab ozogamicin murine analog-mediated B-cell depletion reduces anti-islet allo- and autoimmune responses. Diabetes, 2012 Jan;61(1):155-65. *authors equally contributed to the work
Petrelli A, Carvello M, Vergani A, Lee KM, Du M, Kleffel S, Chengwen L, Mfarrej BG, Hwu P, Secchi A, Leonard W, Young D, Markmann JF, Zajac AJ and Fiorina P. IL-21 is an anti-tolerogenic cytokine of the late-phase alloimmune response. Diabetes, 2011 Dec;60(12):3223-34
