IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in dendritic cells
IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in dendritic cells
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DOI：
10.1016/j.immuni.2005.09.010
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发表时间：
2005-11-01
期刊：
影响因子：
32.4
通讯作者：
Hirano, T
中科院分区：
文献类型：
--
作者：
Kitamura, H;Kamon, H;Hirano, T
我们发现IL-6-STAT3通路抑制树突状细胞（dc）上MHCII类（MHCII）的表达，并减弱T细胞的活化。在这里，我们发现IL-6-STAT3信号传导降低了dc细胞内MHCII α - β二聚体、Ii和H2-DM水平。il -6介导的STAT3激活降低了胱抑素C（一种内源性组织蛋白酶抑制剂）的水平，增强了组织蛋白酶的活性。重要的是，组织蛋白酶S抑制剂阻断了il -6处理的dc中MHCII α - β二聚体、Ii和H2-DM的减少。过度表达胱抑素C抑制il -6- stat3介导的组织蛋白酶S活性升高和MHCII α - β二聚体、Ii和H2-DM水平降低。组织蛋白酶S在dc中的过表达降低了细胞内MHCII α - β二聚体、Ii和H2-DM水平，lps介导的MHCII表面表达和抑制CD4(+) T细胞活化。体内IL-6-gp130-STAT3信号通路降低dc中胱抑素C表达和MHCII α - β二聚体水平。因此，il -6- stat3介导的组织蛋白酶S活性增加降低了dc中MHCII α - β二聚体、Ii和H2-DM水平，并抑制CD4(+) T细胞介导的免疫反应。
We found IL-6-STAT3 pathway suppresses MHC class II (MHCII) expression on dendritic cells (DCs) and attenuates T cell activation. Here, we showed that IL-6-STAT3 signaling reduced intracellular MHCII alpha beta dimmer, Ii, and H2-DM levels in DCs. IL-6-mediated STAT3 activation decreased cystatin C level, an endogenous inhibitor of cathepsins, and enhanced cathepsin activities. Importantly, cathepsin S inhibitors blocked reduction of MHCII alpha beta dimer, Ii, and H2-DM in the IL-6-treated DCs. Overexpression of cystatin C suppressed IL-6-STAT3-mediated increase of cathepsin S activity and reduction of MHCII alpha beta dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII alpha beta dimer, Ii, and H2-DM levels, LPS-mediated surface expression of MHCII and suppressed CD4(+) T cell activation. IL-6-gp130-STAT3 signaling in vivo decreased cystatin C expression and MHCII alpha beta dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII alpha beta dimer, Ii, and H2-DM levels in DCs, and suppresses CD4(+) T cell-mediated immune responses.