One severe complication of celiac disease is enteropathy-associated T cell lymphoma, a high-grade invasive lymphoma with a very poor prognosis. Previous research has suggested that chronic exposure of immune cells in the walls of the small intestine, which are known as intraepithelial lymphocytes, to potent anti-death signals initiated by the soluble factor IL-15 contributes to the development of enteropathy-associated T cell lymphoma.
A team of researchers, at INSERM U989, Université René Descartes, France, has now identified the survival signals delivered by IL-15 to freshly isolated human intraepithelial lymphocytes and to intraepithelial lymphocyte cell lines derived from patients with type II refractory celiac disease -- a clinical state considered an intermediary step between celiac disease and enteropathy-associated T cell lymphoma. Importantly, treatment with an antibody directed at IL-15 caused intraepithelial lymphocytes to die and wiped out their accumulation in mice overexpressing human IL-15 in the lining of their gut.
The team, led by Nadine Cerf-Bensussan and Bertrand Meresse, therefore suggests that IL-15 and its downstream survival signals might provide new targets for the treatment of type II refractory celiac disease.
The research appears in the Journal of Clinical Investigation.
- Malamut et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease–associated inflammation and lymphomagenesis. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI41344
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