Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase

作者: Madhav D. Sharma , Babak Baban , Phillip Chandler , De-Yan Hou , Nagendra Singh

DOI: 10.1172/JCI31911

关键词:

摘要: A small population of plasmacytoid DCs (pDCs) in mouse tumor-draining LNs can express the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO). We show that these IDO+ pDCs directly activate resting CD4+CD25+Foxp3+ Tregs for potent suppressor activity. In vivo, isolated from were constitutively activated and suppressed antigen-specific T cells immediately ex vivo. vitro, rapidly non–tumor-bearing hosts without need mitogen or exogenous anti-CD3 crosslinking. Treg activation by was MHC restricted, required an intact amino acid–responsive GCN2 pathway Tregs, prevented CTLA4 blockade. IDO markedly upregulated programmed cell death 1 ligand (PD-L1) PD-L2 expression on target DCs, ability to suppress proliferation abrogated antibodies against 1/PD-L (PD-1/PD-L) pathway. contrast, crosslinking did not cause upregulation PD-Ls, suppression unaffected blocking PD-1/PD-L vivo showed PD-1/PD-L–mediated suppression, which selectively lost when tumors grown IDO-deficient hosts. hypothesize create a profoundly suppressive microenvironment within via constitutive Tregs.

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