Expression of TCTP antisense in CD25(high) regulatory T cells aggravates cuff-injured vascular inflammation.
This study examines our hypothesis that translationally controlled tumor protein (TCTP) expression in CD4+ CD25(high) regulatory T cells (Tregs) is critical for the interleukin-2 (IL-2) withdrawal-triggered apoptosis pathway in Tregs, and modulation of Treg apoptosis pathway affects development of vascular inflammation. To test this hypothesis, we established a Tregs-specific TCTP antisense transgenic mouse model. Lower TCTP expression in Tregs than in CD4+ CD25- T cells is associated with the higher susceptibility of Tregs to apoptosis induced by IL-2 withdrawal. Overexpression of TCTP antisense in Tregs leads to decreased positive selection of CD25(high) thymic Tregs and reduced survival of peripheral Tregs, which is correlated to our previous report that TCTP antisense knocks-down TCTP protein expression and promotes apoptosis. In addition, TCTP antisense transgene confers higher susceptibility of Tregs to apoptosis induced by IL-2 withdrawal than wild-type Tregs, which can be suppressed by exogenous supply of IL-2, suggesting that IL-2 promotes Treg survival at least partially due to promoting TCTP expression. Finally, decreased expression of TCTP in Tregs aggravates experimental vascular inflammation, presumably due to increased Treg apoptosis and failure of decreased Tregs in suppressing inflammatory cells and immune cells. These results suggest that the modulation of Tregs apoptosis/survival may be used as a new therapeutic approach for inflammatory cardiovascular diseases.
Xiong
Zeyu
Z
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
Yan
Yan
Y
Song
Jian
J
Fang
Pu
P
Yin
Ying
Y
Yang
Yu
Y
Cowan
Alan
A
Wang
Hong
H
Yang
Xiao-Feng
XF
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000235:genetics; D002478:Cells, Cultured; D005263:Femoral Artery / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D019076:Transgenes; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016376:Oligonucleotides, Antisense; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1
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