Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes

Gitanjali Dharmadhikari, Katharina Stolz, Michael Hauke, Noel G Morgan, Ajit Varki, Eelco de Koning, Sørge Kelm, Kathrin Maedler

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore β-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented β-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of β-cell function and survival.

Originele taal-2Engels
Pagina's (van-tot)45319
TijdschriftScientific Reports
Volume7
DOI's
StatusGepubliceerd - 05 apr 2017

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