MHC class II-mediated apoptosis of mature dendritic cells proceeds by activation of the protein kinase C-δ isoenzyme
MHC class II-mediated apoptosis of mature dendritic cells proceeds by activation of the protein kinase C-δ isoenzyme
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DOI：
10.1093/intimm/dxf058
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Mooney, N
中科院分区：
文献类型：
--
作者：
Bertho, N;Blancheteau, VM;Mooney, N
成熟的树突状细胞(DC)被认为是最强大的抗原提呈细胞。因此，对DC的监管，特别是其生存，是至关重要的。成熟DC对人类白细胞抗原DR介导的细胞凋亡的敏感性明显高于未成熟DC。为了进一步表征这一关键的生存差异，我们比较了成熟DC和未成熟DC中通过人类白细胞抗原-DR启动的细胞内信号。抑制酪氨酸激酶或磷酸酶不影响细胞的凋亡。共聚焦显微镜和免疫印迹法检测到成熟DC中的蛋白激酶C(PKC)-Delta在HL A-DR介导下重新定位到细胞核。通过检测成熟DC经人类白细胞抗原DR刺激后分离的核成分中的PKC-Delta催化片段，发现成熟DC中PKC-Delta被激活。广谱PKC抑制剂Calphostin C和PKC-Delta选择性抑制剂Rottlerin可抑制由HLA-DR介导的成熟细胞的凋亡。综上所述，这些数据揭示了PKC-Delta同工酶在调节人类白细胞抗原II类介导的成熟DC的凋亡中的作用。因此，成熟DC的寿命可以通过抗原提呈过程中产生的信号来控制，从而防止DC的持久性和对T、B淋巴细胞的长时间刺激。
The mature dendritic cell (DC) is considered to be the most potent antigen-presenting cell. Regulation of the DC, particularly its survival, is therefore critical. Mature DC are markedly more sensitive to HLA-DR-mediated apoptosis than immature DC. To further characterize this key survival difference, we compared the intracellular signals initiated via HLA-DR in mature versus immature DC. Apoptosis was unchanged by inhibition of tyrosine kinases or phosphatases. HLA-DR-mediated re-localization of protein kinase C (PKC)-delta to the nucleus was detected in mature DC by confocal microscopy and by immunoblotting. Activation of PKC-delta in mature DC was revealed by the detection of the PKC-delta catalytic fragment in the nuclear fraction isolated from mature DC which had been stimulated via HLA-DR. The broad-spectrum PKC inhibitor, Calphostin C, as well as the PKC-delta-selective inhibitor, Rottlerin, inhibited HLA-DR-mediated apoptosis of mature cells. Taken together, these data reveal a role for the PKC-delta isoenzyme in regulating HLA class II-mediated apoptosis of mature DC. Thus, the lifespan of the mature DC could be controlled by signals generated in the course of antigen presentation, and thereby prevent DC persistence and prolonged stimulation of T and B lymphocytes.