Article
Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus
Registro en:
CRUZ, Daniella A. Mendes da; et al. Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus. J Immunol., v.180, p.4639-4647, 2008.
0022-1767
10.4049/jimmunol.180.7.4639
1550-6606.
Autor
Cruz, Daniella A. Mendes da
Smaniotto, Salete
Keller, Alexandre C.
Dardenne, Mireille
Savino, Wilson
Resumen
We previously described a fibronectin/VLA-5-dependent impairment of NOD thymocyte migration, correlated with partial thymocyte
arrest within thymic perivascular spaces. Yet, NOD thymocytes still emigrate, suggesting the involvement of other cell
migration-related alterations. In this context, the aim of this work was to study the role of extracellular matrix ligands, alone or
in combination with the chemokine CXCL12, in NOD thymocyte migration. Intrathymic contents of CXCL12, fibronectin, and
laminin were evaluated by immunohistochemistry while the expression of corresponding receptors was ascertained by flow cytometry.
Thymocyte migration was measured using Transwell chambers and transendothelial migration was evaluated in the same
system, but using an endothelial cell monolayer within the chambers. NOD thymocytes express much lower VLA-5 than C57BL/6
thymocytes. This defect was particularly severe in CD4 thymocytes expressing Foxp3, thus in keeping with the arrest of Foxp3
cells within the NOD giant perivascular spaces. We observed an enhancement in CXCL12, laminin, and fibronectin deposition and
colocalization in the NOD thymus. Furthermore, we detected altered expression of the CXCL12 receptor CXCR4 and the laminin
receptor VLA-6, as well as enhanced migratory capacity of NOD thymocytes toward these molecules, combined or alone. Moreover,
transendothelial migration of NOD thymocytes was diminished in the presence of exogenous fibronectin. Our data unravel
the existence of multiple cell migration-related abnormalities in NOD thymocytes, comprising both down- and up-regulation of
specific responses. Although remaining to be experimentally demonstrated, these events may have consequences on the appearance
of autoimmunity in NOD mice. 2030-01-01