Journal article

Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes

Federica Vecchio, Nicola Lo Buono, Angela Stabilini, Laura Nigi, Matthew J Dufort, Susan Geyer, Paola Maria Rancoita, Federica Cugnata, Alessandra Mandelli, Andrea Valle, Pia Leete, Francesca Mancarella, Peter S Linsley, Lars Krogyold, Keyan C Herold, Helena Elding Larsson, Sarah J Richardson, Noel G Morgan, Knut Dahl-Jorgensen, Guido Sebastiani Show all

JCI Insight | AMER SOC CLINICAL INVESTIGATION INC | Published : 2018

Abstract

BACKGROUND: Neutrophils and their inflammatory mediators are key pathogenic components in multiple autoimmune diseases, while their role in human type 1 diabetes (T1D), a disease that progresses sequentially through identifiable stages prior to the clinical onset, is not well understood. We previously reported that the number of circulating neutrophils is reduced in patients with T1D and in presymptomatic at-risk subjects. The aim of the present work was to identify possible changes in circulating and pancreas-residing neutrophils throughout the disease course to better elucidate neutrophil involvement in human T1D. METHODS: Data collected from 389 subjects at risk of developing T1D, and enr..

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University of Melbourne Researchers

Grants

Awarded by Juvenile Diabetes Research Foundation (JDRF)


Awarded by Diabetes UK


Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development


Awarded by Network for Pancreatic Organ donors with Diabetes (nPOD)


Awarded by JDRF


Awarded by Leona M. & Harry B. Helmsley Charitable Trust



Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

We thank all the donors and the medical staff who made this study possible. We thank Alessandra Petrelli and all the MB laboratory (San Raffaele Diabetes Research Institute, Milan) for fruitful scientific discussion. We are grateful to Irene Gotuzzo and Benedetta Pessina for sample and clinical data collection (Universita Vita e Salute, Milan). We thank Birgit Sawitzki and Jochen Hecht (Charite Universitatsmedizin, Berlin) for assisting with RNA-seq data generation and Giovanni Malerba (Universita di Verona, Italy) for assisting with the first RNA-seq data analysis. We thank Benedetta Allegra Mazzi (San Raffaele Hospital) for HLA genotyping. We thank the Advanced Light and Electron Microscopy BioImaging Center (ALEMBIC) (especially Cesare Covino, Desiree Zambroni, and Valeria Berno) of the San Raffaele Scientific Institute and Vita-Salute University for assisting in some of the imaging work. See Supplemental Acknowledgments for consortium details. This work was in part supported by Juvenile Diabetes Research Foundation (JDRF) grants RSA-206-262-S-B to MB and 5-CDA-2014-221-A-N to SJR; and by Diabetes UK (15/0005156) to NGM and SJR. The sponsor of the trials was the Type 1 Diabetes TrialNet Study Group. Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the NIH through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK085476, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, and the JDRF. The contents of this Article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF. This research was performed with the support of the Network for Pancreatic Organ donors with Diabetes (nPOD; RRID:SCR_014641), a collaborative type 1 diabetes research project sponsored by the JDRF (nPOD: 5-SRA-2018-557-Q-R) and The Leona M. & Harry B. Helmsley Charitable Trust (grant 2018PG-T1D053). Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org//for-partners/npod-partners/.