Gene expression profiles for the human pancreas and purified islets in Type 1 diabetes: new findings at clinical onset and in long-standing diabetes
Raquel Planas,Jorge Carrillo,Alex Sánchez,Alex Sánchez,M. C. Ruiz de Villa,F Nuñez,Joan Verdaguer,Roger F.L. James,Ricardo Pujol-Borrell,Marta Vives-Pi +9 more
TLDR
In this paper, the authors reported whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four Type 1 diabetes patients and for purified islets from two of them.Abstract:
Type 1 diabetes (T1D) is caused by the selective destruction of the insulin-producing beta cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. non-classical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.read more
Citations
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Peripheral and Islet Interleukin-17 Pathway Activation Characterizes Human Autoimmune Diabetes and Promotes Cytokine-Mediated β-Cell Death
Sefina Arif,Fabrice Moore,Katherine Marks,Thomas Bouckenooghe,Colin M. Dayan,Raquel Planas,Marta Vives-Pi,Jake Powrie,Timothy Tree,Piero Marchetti,Guo Cai Huang,Esteban Nicolas Gurzov,Ricardo Pujol-Borrell,Decio L. Eizirik,Mark Peakman +14 more
TL;DR: It is shown that IL-17 mediates significant and reproducible enhancement of IL-1β/interferon (IFN)-γ–induced and tumor necrosis factor (TNF)-α/IFN-γ-induced apoptosis in human islets, rat β-cells, and INS-1E cells, in association with significant upregulation of β-cell IL17RA expression via activation of the transcription factors STAT1 and nuclear factor (NF)-κB.
Journal ArticleDOI
Insulitis in human type 1 diabetes: The quest for an elusive lesion.
TL;DR: Recent new insights into the regenerative capacity of the β-cell mass in the pre-clinical stages of the disease are discussed and these findings to the inflammatory processes within the islet tissue are related.
Journal ArticleDOI
Islet inflammation and CXCL10 in recent-onset type 1 diabetes.
Bart O. Roep,F. S. Kleijwegt,A. G. S. van Halteren,Vittoria Bonato,Ugo Boggi,Francesco Vendrame,Piero Marchetti,Francesco Dotta +7 more
TL;DR: The data point to CXCL10 as an important cytokine in distressed islets that may contribute to inflammation leading to insulitis and β cell destruction, regardless of local viral infection.
Journal ArticleDOI
Plasma-derived exosome characterization reveals a distinct microRNA signature in long duration Type 1 diabetes.
Marta Garcia-Contreras,Marta Garcia-Contreras,Sanket Shah,Alejandro Tamayo,Paul D. Robbins,Ronald B. Golberg,Armando J. Mendez,Camillo Ricordi +7 more
TL;DR: The potential of EXOs miRNA profiling in the diagnosis of type 1 diabetes mellitus is highlighted as well as new insights into the molecular mechanisms involved in T1DM are revealed.
Journal ArticleDOI
The role of the complement system in metabolic organs and metabolic diseases
TL;DR: The link between complement and metabolic organs, focusing on the pancreas, adipose tissue, and liver and the diverse effects of complement system on metabolic disorders are discussed.
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