Butyrophilin Btn2a2 inhibits TCR activation and phosphatidylinositol 3-kinase/Akt pathway signaling and induces Foxp3 expression in T lymphocytes.
Butyrophilin Btn2a2 inhibits TCR activation and phosphatidylinositol 3-kinase/Akt pathway signaling and induces Foxp3 expression in T lymphocytes.
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DOI：
10.4049/jimmunol.1203325
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发表时间：
2013-05-15
期刊：
影响因子：
--
通讯作者：
Trowsdale J
中科院分区：
文献类型：
--
作者：
Ammann JU;Cooke A;Trowsdale J
小鼠CD19+B细胞、CD11b+F4/80+巨噬细胞和CD11c+骨髓来源的树突状细胞经脂多糖或Pam3CysK4激活后，Btn2a2表达上调，提示Btn2a2在T淋巴细胞的调节中起作用。与此一致的是，在抗CD3和抗CD28的刺激下，小鼠Btn2a2-Fc与CD3+原代小鼠T细胞的结合减少了增殖细胞的数量和进入细胞周期的细胞。Btn2a2-Fc与抗CD3−刺激的T细胞的结合抑制了CD3ZAP70和随后的ERK1/2的激活。它还干扰在抗CD3和抗CD28刺激的T细胞中PI3K、P85调节亚基的激活和Akt的激活。与PD-L1-Fc相比，Btn2a2-Fc对Akt激活的抑制不能被抗CD28共刺激所克服。利用Foxp3-GFP转基因小鼠T细胞，Btn2a2-Fc以剂量依赖方式诱导Foxp3从头表达，Btn2a2-Fc诱导的CD4+CD25+Foxp3+T细胞具有抑制作用。提示Btn2a2在抑制T细胞活化和诱导Foxp3+调节性T细胞方面具有重要的生理作用。
The butyrophilin-related protein Btn2a2 was up-regulated on murine antigen presenting cells including CD19+ B cells, CD11b+ F4/80+ peritoneal macrophages, and CD11c+ bone marrow-derived dendritic cells after activation with LPS or Pam3CysK4, suggesting a role in modulation of T lymphocytes. Consistent with this, binding of mouse Btn2a2-Fc to CD3+ primary mouse T cells stimulated with anti-CD3 and anti-CD28 reduced the number of proliferating cells and entry of cells into the cell cycle. Binding of Btn2a2-Fc to anti-CD3− stimulated T cells inhibited CD3ε, Zap70, and subsequent Erk1/2 activation. It also interfered with activation of the regulatory subunit of PI3K, p85, and activation of Akt in T cells stimulated with both anti-CD3 and anti-CD28. Inhibition of Akt activation by Btn2a2-Fc was, in contrast to inhibition by PD-L1-Fc, not overcome by anti-CD28 co-stimulation. Using Foxp3-GFP transgenic, naïve T cells, Btn2a2-Fc induced de novo expression of Foxp3 in a dose-dependent manner and Btn2a2-Fc-induced CD4+CD25+Foxp3+ T cells had inhibitory properties. The data indicate an important physiological role for Btn2a2 in inhibiting T cell activation and inducing Foxp3+ regulatory T cells.
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影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1073/pnas.1010647108
发表时间：
2011-03-15
影响因子：
11.1
作者：
Bas, Anna;Swamy, Mahima;Hayday, Adrian C.
通讯作者：
Hayday, Adrian C.
影响因子：
3.7
作者：
Huber S;Schrader J;Fritz G;Presser K;Schmitt S;Waisman A;Lüth S;Blessing M;Herkel J;Schramm C
通讯作者：
Schramm C
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ