The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema
The importance of myeloid-derived suppressor cells in the regulation of autoimmune effector cells by a chronic contact eczema
复制标题
DOI：
10.4049/jimmunol.179.8.5071
复制
发表时间：
2007-10-15
影响因子：
4.4
通讯作者：
Zoeller, Margot
中科院分区：
文献类型：
--
作者：
Marhaba, Rachid;Vitacolonna, Mario;Zoeller, Margot
诱导慢性湿疹是治疗斑秃最有效的方法。我们已经注意到AA诱导过程中调节性T细胞的减少，并想知道调节性T细胞是否可能在反复皮肤致敏过程中被招募或扩增，或者额外的调节性细胞是否导致毛发再生。从接触致敏剂反复治疗的小鼠中转移CD 4（+）CD 25（高）淋巴结细胞不能治愈AA。这显然是与调节性CD 4（+）D25（+）T细胞相比，新鲜活化细胞占优势的结果。相反，在用接触致敏剂反复处理的AA小鼠的皮肤和脾脏中，Gr 1（+）D11 b（+）细胞群显著增加。Gr-1（+）11b（+）脾细胞主要表达CD 31。几种促炎细胞因子以及IFN-γ受体和TNF受体I的表达增加。特别是在皮肤中，Gr-1（+）细胞高水平表达几种趋化因子和CCR 8。Gr-1（+）CD 11b（+）细胞在体外最有效地抑制AA效应细胞增殖，并在体内促进部分毛发再生。当与AA小鼠的CD 4（+）或CD 8（+）细胞共培养时，Gr-1（+）CD 11b（+）细胞分泌高水平的NO，但可能由于AA T细胞中高水平的Bcl-2蛋白表达，其凋亡诱导没有改变。相反，zeta链表达强烈下调，这是伴随着ZAP 70和ERK 1/2磷酸化的减少。因此，慢性湿疹支持骨髓抑制细胞的扩增和活化，其通过ζ链下调，有助于体外和体内自身反应性T细胞沉默。
Induction of a chronic eczema is a most efficient therapy for alopecia areata (AA). We had noted a reduction in regulatory T cells during AA induction and wondered whether regulatory T cells may become recruited or expanded during repeated skin sensitization or whether additional regulatory cells account for hair regrowth. AA could not be cured by the transfer of CD4(+)CD25(high) lymph node cells from mice repeatedly treated with a contact sensitizer. This obviously is a consequence of a dominance of freshly activated cells as compared with regulatory CD4(+)D25(+) T cells. Instead, a population of Gr1(+)D11b(+) cells was significantly increased in skin and spleen of AA mice repeatedly treated with a contact sensitizer. Gr-1(+)11b(+) spleen cells mostly expressed CD31. Expression of several proinflammatory cytokines as well as of the IFN-gamma receptor and the TNF receptor I were increased. Particularly in the skin, Gr-1(+) cells expressed several chemokines and CCR8 at high levels. Gr-1(+)CD11b(+) cells most potently suppressed AA effector cell proliferation in vitro and promoted partial hair regrowth in vivo. When cocultured with CD4(+) or CD8(+) cells from AA mice, the Gr-1(+)CD11b(+) cells secreted high levels of NO. However, possibly due to high level Bcl-2 protein expression in AA T cells, apoptosis induction remained unaltered. Instead, zeta-chain expression was strongly down-regulated, which was accompanied by a decrease in ZAP70 and ERK1/2 phosphorylation. Thus, a chronic eczema supports the expansion and activation of myeloid suppressor cells that, via zeta-chain down-regulation, contribute to autoreactive T cell silencing in vitro and in vivo.