Unknown

Dataset Information

0

IL-18 is required for self-reactive T cell expansion in NOD mice.


ABSTRACT: IL-18 has a well-established role in pro-inflammatory responses in the islets in type 1 diabetes. Here, we identify a distinctive role for IL-18 in expanding pathogenic T cells in the periphery of NOD mice. Well in advance of disease onset, the periphery of IL-18-deficient mice exhibits reduced T cell turnover, an increased prevalence of naïve and quiescent T cells, emergence of fewer effector T cells, and disease protection. Islet-reactive T cells fail to become activated in the lymphoid organs of mice lacking IL-18 and their rapid expansion is inhibited. IL-18 secretion by antigen presenting cells increases with advancing disease and is required for expression of its receptor on T cells. Our results demonstrate that induction of the IL-18 receptor reflects a critical stage of autoreactive T cell activation and expansion on the pathway toward effector T cell differentiation. This study therefore assigns a novel role to IL-18 for expanding the pool of islet-destructive T cells during pre-diabetes. This report highlights a new basic mechanism in type 1 diabetes pathogenesis and suggests that targeting the IL-18 pathway should be explored as a potential treatment strategy.

SUBMITTER: Marleau AM 

PROVIDER: S-EPMC4275030 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

IL-18 is required for self-reactive T cell expansion in NOD mice.

Marleau Annette M AM   Sarvetnick Nora E NE  

Journal of autoimmunity 20110316 3-4


IL-18 has a well-established role in pro-inflammatory responses in the islets in type 1 diabetes. Here, we identify a distinctive role for IL-18 in expanding pathogenic T cells in the periphery of NOD mice. Well in advance of disease onset, the periphery of IL-18-deficient mice exhibits reduced T cell turnover, an increased prevalence of naïve and quiescent T cells, emergence of fewer effector T cells, and disease protection. Islet-reactive T cells fail to become activated in the lymphoid organs  ...[more]

Similar Datasets

| S-EPMC5233468 | biostudies-literature
| S-EPMC123148 | biostudies-literature
| S-EPMC4323636 | biostudies-literature
| S-EPMC3251096 | biostudies-literature
| S-EPMC4165707 | biostudies-literature
| S-EPMC8234286 | biostudies-literature
| S-EPMC4206736 | biostudies-literature
| S-EPMC7068803 | biostudies-literature
| S-EPMC7688534 | biostudies-literature
| S-EPMC8409809 | biostudies-literature