Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans

A. Olivieri, S. De Angelis, S. Dionisi, G. D'Annunzio, M. Locatelli, M. Marinaro, V. Bonato, A. Amendola, M. Songini, F. Velluzzi, C. Schirru, R. Cotichini, M. A. Stazi, F. Dotta, R. Lorini, G. F. Bottazzo, M. Boirivant

Research output: Contribution to journalArticlepeer-review

Abstract

Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D.

Original languageEnglish
Pages (from-to)407-414
Number of pages8
JournalClinical and Experimental Immunology
Volume162
Issue number3
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Insulitis
  • NOD mice
  • Prediabetes
  • TGF-b1
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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