Innate inflammation in type 1 diabetes. Transl Res 2016 Jan;167(1):214-27
Date
05/20/2015Pubmed ID
25980926Pubmed Central ID
PMC4626442DOI
10.1016/j.trsl.2015.04.011Scopus ID
2-s2.0-84952638473 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Type 1 diabetes mellitus (T1D) is an autoimmune disease often diagnosed in childhood that results in pancreatic β-cell destruction and life-long insulin dependence. T1D susceptibility involves a complex interplay between genetic and environmental factors and has historically been attributed to adaptive immunity, although there is now increasing evidence for a role of innate inflammation. Here, we review studies that define a heightened age-dependent innate inflammatory state in T1D families that is paralleled with high fidelity by the T1D-susceptible biobreeding rat. Innate inflammation may be driven by changes in interactions between the host and environment, such as through an altered microbiome, intestinal hyperpermeability, or viral exposures. Special focus is put on the temporal measurement of plasma-induced transcriptional signatures of recent-onset T1D patients and their siblings as well as in the biobreeding rat as it defines the natural history of innate inflammation. These sensitive and comprehensive analyses have also revealed that those who successfully managed T1D risk develop an age-dependent immunoregulatory state, providing a possible mechanism for the juvenile nature of T1D. Therapeutic targeting of innate inflammation has been proven effective in preventing and delaying T1D in rat models. Clinical trials of agents that suppress innate inflammation have had more modest success, but efficacy may be improved by the addition of combinatorial approaches that target other aspects of T1D pathogenesis. An understanding of innate inflammation and mechanisms by which this susceptibility is both potentiated and mitigated offers important insight into T1D progression and avenues for therapeutic intervention.
Author List
Cabrera SM, Henschel AM, Hessner MJAuthors
Susanne M. Cabrera MD Associate Professor in the Pediatrics department at Medical College of WisconsinMartin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsDiabetes Mellitus, Type 1
Disease Models, Animal
Humans
Immunity, Innate
Inflammation
Rats