Functional capacity of macrophages determines the induction of type 1 diabetes.
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 beta-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 beta 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.
Mensah-Brown
Epk
E
Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al Ain, United Arab Emirates.
Shahin
A
A
Parekh
Khatija
K
Hakim
A Al
AA
Shamisi
M Al
MA
Hsu
D K
DK
Lukic
M L
ML
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology*; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology
D037502:Galectin 3