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

TY - JOUR

T1 - Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes

AU - Dharmadhikari, Gitanjali

AU - Stolz, Katharina

AU - Hauke, Michael

AU - Morgan, Noel G

AU - Varki, Ajit

AU - de Koning, Eelco

AU - Kelm, Sørge

AU - Maedler, Kathrin

PY - 2017/4/5

Y1 - 2017/4/5

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/srep45319

DO - 10.1038/srep45319

M3 - Article

C2 - 28378743

SN - 2045-2322

VL - 7

SP - 45319

JO - Scientific Reports

JF - Scientific Reports

ER -