TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in nonobese diabetic mice.
TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in nonobese diabetic mice.
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TLR9缺乏促进了非肥胖糖尿病小鼠T细胞和糖尿病保护中的CD73表达。
DOI：
10.4049/jimmunol.1300547
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发表时间：
2013-09-15
期刊：
影响因子：
--
通讯作者：
Wen L
中科院分区：
文献类型：
--
作者：
Tai N;Wong FS;Wen L
TLR9-/-NOD mice develop a significantly reduced incidence of diabetes. This study was to investigate the molecular mechanisms of the protective role of TLR9 deficiency. Through gene screening and confirmation by both mRNA and protein expression, we found a significant increase in CD73-expressing immune cells from peripheral lymphoid tissues in TLR9-/-NOD mice. The elevated frequency of CD73-expressing immune cells seemed to be specific for TLR9 deficiency and was MyD88-independent. Moreover, the increased frequency of CD73 expression was limited to the NOD background. Increased frequency of CD73 expression was also associated with lower levels of pro-inflammatory cytokines and more anti-inflammatory cytokine production in CD4+ T cells in TLR9-/-NOD mice. Purified CD73+CD4+ T cells showed stronger immunosuppressive function in vitro and delayed diabetes development in vivo. The immunosuppression appeared to be mediated by TGFβ. In addition, elevated frequency of CD73 expressing cells was associated with improved β cell function. Our observations were further confirmed by protection from diabetes with similar alterations in CD73 in the NY8.3 T cell receptor (TCR) NOD mouse model crossed with TLR9 deficient mice and by the use of a TLR9 inhibitor in NOD mice. Our novel findings suggest an important immune regulatory role of CD73 in regulation of diabetes development and may offer a new therapeutic strategy for specific intervention to prevent T1D.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
影响因子：
20.1
作者：
Hasegawa T;Bouïs D;Liao H;Visovatti SH;Pinsky DJ
通讯作者：
Pinsky DJ
影响因子：
4.4
作者：
Lampropoulou, Vicky;Hoehlig, Kai;Fillatreau, Simon
通讯作者：
Fillatreau, Simon
影响因子：
3.7
作者：
Aumeunier A;Grela F;Ramadan A;Pham Van L;Bardel E;Gomez Alcala A;Jeannin P;Akira S;Bach JF;Thieblemont N
通讯作者：
Thieblemont N
DOI：
10.1084/jem.188.8.1433
发表时间：
1998-10-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lennon PF;Taylor CT;Stahl GL;Colgan SP
通讯作者：
Colgan SP