CXCL12 enhances exogenous CD4+CD25+ T cell migration and prevents embryo loss in non-obese diabetic mice.
OBJECTIVE
To investigate the possible role of CXCL12 in the migration of regulatory T (Treg) cells.


METHODS
Animal model-based study.


METHODS
Academic.


METHODS
Pregnant non-obese diabetic (NOD) mice were compared with non-immunodeficient mice.


METHODS
In vivo and in vitro CXCL12 induction.


METHODS
Flow cytometric analysis and Treg cell migratory assay.


RESULTS
A significantly high percentage of spontaneous embryo resorption was observed in both syngeneic and allogeneic pregnant NOD mice. The percentage of embryo loss in allogeneic pregnant NOD mice was significantly decreased by treatment with Treg cells and CXCL12 injection; however, no such effect was observed in syngeneic pregnant NOD mice. In addition, the migration of Treg cells induced by CXCL12 was confirmed by both in vitro and in vivo migratory assays. CXCR4, the specific receptor for CXCL12, was expressed more intensively on Treg cells than on non-Treg CD3(+) T cells, whereas CXCL12 was dominantly expressed in cytokeratin 7(+) trophoblast cells at an early stage of gestation, and its expression reduced gradually during pregnancy.


CONCLUSIONS
The higher level of embryo loss in allogeneic pregnant NOD mice may be due to the lack of Treg cells. CXCL12 can cause CXCR4(+) Treg cells to migrate into the pregnant uterus and establish a beneficial microenvironment for the fetus.
Lin
Yi
Y
Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou, People's Republic of China.
Xu
Liang
L
Jin
Haiyan
H
Zhong
Yanmin
Y
Di
Jingfang
J
Lin
Qi-de
QD
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002465:Cell Movement; D054426:Chemokine CXCL2 / Q000276:immunology*; D005260:Female; D005313:Fetal Death / Q000276:immunology / Q000517:prevention & control; D005327:Fetal Resorption / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit