Fibronectin receptor defects in NOD mouse leucocytes: possible consequences for type 1 diabetes

Scandinavian Journal of Immunology
S B GeutskensWilson Savino

Abstract

Integrins of the very late antigen (VLA) family mediate leucocyte traffic to lymphoid organs under physiological conditions and in chronic inflammatory situations such as autoimmunity. Accordingly, the current thinking is of a positive correlation between VLA expression and capability of the generation of autoimmunity. Herein we discuss recent findings on the defective expression of integrin-type fibronectin receptors alpha4beta1 (VLA-4) and alpha5beta1 (VLA-5) in the non-obese diabetic (NOD) mouse, a murine model of autoimmune insulin-dependent diabetes mellitus. As compared with normal animals, NOD thymocytes (including the CD4+CD25+ regulatory T cells) exhibit a decrease in the membrane expression of alpha5beta1, resulting in a functional impairment of fibronectin-mediated interactions, including cell migration. Interestingly, thymocytes that are trapped within the giant perivascular spaces seen in NOD thymus are consistently alpha5beta1 negative, suggesting that the progressive arrest of mature cells can be related to the alpha5beta1 defect. Peripheral T cells also exhibit decreased alpha5beta1 membrane expression and impaired fibronectin-driven migration. Additionally, we observed a defect in alpha4beta1 fibronectin recept...Continue Reading

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Citations

Mar 2, 2010·Immunobiology·Patrícia R A NagibLiana Verinaud
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniella A Mendes-da-CruzWilson Savino
May 15, 2018·International Journal of Molecular Sciences·Julia P LemosDaniella A Mendes-da-Cruz

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