Tumor-derived immuno-modulators induce overlapping pro-tolerogenic gene expression signatures in human dendritic cells

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• 作者：Stefanie Trojandt ; Iris Bellinghausen ; Angelika B. Reske-Kunz ; Matthias Bros ; ^{mbros@uni-mainz.de}
• 关键词：Dendritic cells ; Tolerogenic ; Dexamethason ; Interleukin-10 ; Prostaglandin E2
• 刊名：Human Immunology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：77
• 期：12
• 页码：1223-1231
• 全文大小：938 K
• 卷排序：77

文摘

Immature dendritic cells (iDCs) and tolerogenic DCs are essential for the induction and maintenance of peripheral tolerance. Tumors produce immuno-modulatory factors which imprint a pro-tolerogenic, maturation-resistant state in DCs. Here we asked for common markers of differentially tolerized human monocyte-derived DC populations. For this, PBMC-derived monocytes were differentiated to DCs in the presence of established immuno-modulators as released by tumors (IL-6, IL-10, TGF-β, glucocorticoid [GC], prostaglandin E2 [PGE2]). Most unstimulated pro-tolerogenic DC populations commonly over-expressed some tolerance-associated markers (ILT-4, IL-10, HO-1) as compared with iDCs. These markers may contribute to imprint a pro-tolerogenic state in DCs. Furthermore, some tolerance markers were overexpressed in an immuno-modulator specific manner in DCs differentiated in the presence of TGF-β (overexpressed tolerance markers: B7-H3, CD103, TGF-β1), IL-10 (B7-DC, ILT-3) and PGE2 (IDO). Upon stimulation, matured control DCs (mDCs) down-regulated most pro-tolerogenic markers monitored, while some were upregulated (IkBα, IDO, B7-H1, B7-DC). In contrast, the different groups of tolerized DCs largely retained expression of pro-tolerogenic markers after stimulation. In contrast to mDCs, most groups of tolerized DCs showed impaired upregulation of CD80, and all groups retained IL-10 cytokine production after stimulation. All tolerized DC populations commonly exerted an attenuated allogenic T cell stimulatory capacity as compared with mDCs.