| dc.description | Previous work revealed the existence of a severe
thymic atrophy with massive loss of immature CD4+CD8+
thymocytes in animals developing insulin-dependent diabetes,
chemically induced by alloxan. Furthermore, the intrathymic
expression of chemokines, such as CXCL12, is
changed in these animals, suggesting that cell migrationrelated
patterns may be altered. One molecular interaction
involved in normal thymocyte migration is that mediated by
soluble semaphorin-3A and its cognate receptor neuropilin-
1. Objectives: We investigated herein the expression and
role of semaphorin-3A in the migratory responses of thymocytes
from alloxan-induced diabetic mice. We characterized
semaphorin-3A and its receptor, neuropilin-1, in thymuses
from control and diabetic mice as well as semaphorin-3Adependent
migration of developing thymocytes in both
control and diabetic animals. Methods: Diabetes was chemically
induced after a single injection of alloxan in young
adult BALB/c mice. Thymocytes were excised from control
and diabetic individuals and subjected to cytofluorometry
for simultaneous detection of semaphorin-3A or neuropilin-
1 in CD4/CD8-defined subsets. Cell migration in response
to semaphorin-3A was performed using cell migration transwell
chambers. Results: Confirming previous data, we observed
a severe decrease in the total numbers of thymocytes
in diabetic mice, which comprised alterations in both immature
(double-negative subpopulations) and mature CD4/
CD8-defined thymocyte subsets. These were accompanied
by a decrease in the absolute numbers of semaphorin-3Abearing
thymocytes, comprising CD4–CD8–, CD4+CD8+, and
CD4–CD8+ cells. Additionally, immature CD4–CD8– and
CD4+CD8+ developing T cells exhibited a decrease in the
membrane density of semaphorin-3A. The relative and absolute
numbers of neuropilin-1-positive thymocytes were also
decreased in diabetic mouse thymocytes compared to controls,
as seen in CD4–CD8–, CD4+CD8+, and CD4–CD8+ cell
subpopulations. Functionally, we observed a decrease in the SEMA-3A: Reduction of Thymocyte
Migration in Chemically Induced Diabetic
Mice
Neuroimmunomodulation 2020;27:28–37 29
DOI: 10.1159/000506054
chemorepulsive role of semaphorin-3A, as revealed by transwell
migration chambers. Such an effect was seen in all immature
and mature thymocyte subsets.. | |
