The Pancreatic Macrophage Compartment in Health and autoimmune Diabetes: a study on Maturation, Mobility and Matrix interactions
Year: 2004
Type: dissertation
Abstract: Type 1 diabetes is a disease that results from a disturbed glucose metabolism \ndue to a deficiency in insulin production. This deficiency is the consequence of immune-\nmediated damage to the insulin-producing ß-cells. The cause of type 1 diabetes is \npresently unknown and probably multifactorial. The initiation and progression of the \ninflammatory process that destroys the ß-cells involves the interplay of environmental \nfactors with an autoimmune-prone genetic background. Abnormal immune regulation \nexplains the autoimmune phenomena observed in diabetic patients and in spontaneous \nanimal models for the disease to a limited extent only. The precise reason for the \nimmune system to target the pancreatic islets of Langerhans is still unclear. \n\nThe pathogenic process in the pancreas is characterized by the pathology-\nrelated intra-islet infiltration of T and B-lymphocytes that mediate islet destruction. This T \nand B-cell infiltration is preceded by an accumulation of macrophages and dendritic cells \nat the islet periphery. The early peri-islet accumulation of these antigen presenting cells \nprobably reflects the first response of the immune system that is progressively heading \nfor islet destruction. \n\nMacrophages are involved in every step of the diabetogenic process. In the non-\nobese diabetic (NOD) mouse that spontaneously develops diabetes, various \nmacrophage-abnormalities like defective maturation, reduced phagocytosis and \nincreased production of IL-12, have been described previously. Moreover, macrophages \nare present in higher numbers in the pancreas of the NOD mouse from birth onwards, \nrandomly distributed in the connective tissue and ex
Author: Sacha B. Geutskens
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Award: G3471726194
OpenAlex ID: W2170880244