IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines
IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines
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DOI：
10.4049/jimmunol.165.3.1395
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发表时间：
2000-08-01
影响因子：
4.4
通讯作者：
Girolomoni, G
中科院分区：
文献类型：
--
作者：
Albanesi, C;Scarponi, C;Girolomoni, G
ifn诱导的10 kDa蛋白（IP-10）， ifn - γ (Mig)诱导的单因子，ifn诱导的T细胞α -趋化因子（I-TAC）属于非谷氨酸-亮氨酸-精氨酸基元CXC趋化因子家族，仅通过CXCR3受体作用于T淋巴细胞的有效吸引。在本研究中，我们评估了T细胞来源的细胞因子IL-4， IL-10和IL-17调节IP-10， Mig，IL-4，而非IL-10或IL-17，显著上调ifn - γ或tnf - α诱导的角质形成细胞中IP-10、Mig和I-TAG mRNA的积累，并增加角质形成细胞上清液中IP-10和Mig的水平。ACD皮肤免疫组化结果显示，约70%的浸润细胞对CXCR3有反应，且CXCR3染色共定位于CD4（+）和CD8(+) T细胞。从ACD皮肤中建立的镍特异性CD4（+）和CD8(+) T细胞系产生ifn - γ和IL-4，并表达中高水平的CXCR3。最后，受刺激的角质形成细胞释放的CXCR3激动性趋化因子触发皮肤源性镍特异性CD4(+) T细胞的钙动员并促进其迁移。用ifn - γ和IL-4刺激角质形成细胞培养的上清比单独用ifn - γ激活的角质形成细胞的上清更有效地吸引。总之，IL-4通过增强ifn - γ和tnf - α诱导IP-10、Mig和I-TAG对角质形成细胞发挥促炎功能，这反过来可能决定了炎症反应部位CXCR3(+) T淋巴细胞的显著募集。
IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC) belong to the non-glutamate-leucine-arginine motif CXC chemokine family and act solely through the CXCR3 receptor for potent attraction of T lymphocytes, In this study, we evaluated the capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP-10, Mig, and I-TAG in cultured human keratinocytes and CXCR3 expression in T cells from allergic contact dermatitis (ACD), IL-4, but not IL-10 or IL-17, significantly up-regulated IFN-gamma- or TNF-alpha-induced IP-10, Mig, and I-TAG mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in keratinocyte supernatants, Immunohistochemistry of skin affected by ACD revealed that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining colocalized in CD4(+) and CD8(+) T cells. Nickel-specific CD4(+) and CD8(+) T cell lines established from ACD skin produced IFN-gamma and IL-4 and expressed moderate to high levels of CXCR3, Finally, CXCR3 agonistic chemokines released by stimulated keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4(+) T cells and promoted their migration, with supernatant from keratinocyte cultures stimulated with IFN-gamma and IL-4 attracting more efficaciously than supernatant from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha induction of IP-10, Mig, and I-TAG, which in turn may determine a prominent recruitment of CXCR3(+) T lymphocytes at inflammatory reaction sites.