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Functional Capacity of Macrophages Determines the Induction of Type 1 Diabetes
Author(s) -
MENSAHBROWN EPK,
SHAHIN A.,
PAREKH KHATIJA,
HAKIM A. AL,
SHAMISI M. AL,
HSU D.K.,
LUKIC M.L.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1372.014
Subject(s) - insulitis , autoimmunity , islet , immune system , galectin , immunology , galectin 1 , biology , pancreatic islets , microbiology and biotechnology , diabetes mellitus , endocrinology
Abstract: Macrophages are potent immune regulators and are critical in the development and pathogenesis of autoimmune diabetes. They are said to be the first cell type to infiltrate the pancreatic islet, serve as antigen‐presenting cells, and are important as effector cells during diabetogenesis. The article examines the role of macrophages in autoimmune diabetes with particular emphasis on the role of galectin‐3, a β‐galactoside‐binding lectin, and T1/ST2, an IL‐1 receptor‐like protein, both of which play significant roles in the immunomodulatory functions of macrophages. Multiple low‐dose streptozotocin (MLD‐STZ) induces infiltration of mononuclear cells in the islets of susceptible strains leading to insulitis. Deletion of the galectin‐3 gene from C57BL/6 mice significantly attenuates this effect as evaluated by quantitative histology of mononuclear cells and loss of insulin‐producing β cells. In contrast, deletion of the ST2 gene enhanced insulitis after MLD‐STZ treatment when compared with relatively resistant wild‐type BALB/c mice. Thus, it appears that functional capacity of macrophages influences their participation in T helper (Th) 1‐mediated autoimmunity and the development of autoimmune diabetogenesis.