PMID- 24366217 OWN - NLM STAT- MEDLINE DCOM- 20140924 LR - 20171116 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 9 IP - 3 DP - 2014 Mar TI - Increased expression of herpesvirus entry mediator in 1,25-dihydroxyvitamin D3-treated mouse bone marrow-derived dendritic cells promotes the generation of CD4(+)CD25(+)Foxp3(+) regulatory T cells. PG - 813-8 LID - 10.3892/mmr.2013.1874 [doi] AB - Dendritic cells (DCs) can initiate immune responses or induce immune tolerance. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that can induce tolerogenic dendritic cells favoring the induction of regulatory T cells (Treg). The present study revealed a tolerogenic effect of 1,25(OH)2D3 on the phenotype and function of ovalbumin (OVA)‑activated mouse bone marrow‑derived DCs. Three inhibitory molecules associated with tolerogenic DCs, programmed death‑ligand-1 (PD‑L1), PD‑L2 and herpesvirus entry mediator (HVEM) and the expression of co‑stimulatory molecules (CD80, CD86 and CD40) on 1,25(OH)2D3‑treated DCs were examined. The levels of interleukin (IL)‑2, IL‑6 and IL‑10 secreted by 1,25(OH)2D3‑treated DCs were analyzed. The capability of 1,25(OH)2D3‑treated DCs to induce CD4+CD25+Foxp3+ Treg and the stimulation of allogeneic CD4+ T‑cell proliferation in mixed lymphocyte reaction (MLR) was studied. 1,25(OH)2D3‑treated DCs induced up to 21.0‑fold upregulation of the HVEM expression and 4.1‑fold enhancement of the HVEM expression upon activation with OVA [OVA‑D3/immature (im)DCs]. PD‑L1 was not affected by 1,25(OH)2D3‑treated DCs and downregulated PD‑L2 expression on 1,25(OH)2D3‑treated DCs and OVA‑D3/imDC. The expression of co‑stimulatory molecules (CD80, CD86 and CD40) was downregulated in 1,25(OH)2D3‑treated DCs and OVA‑D3/imDC. Furthermore, 1,25(OH)2D3‑treated DCs secreted much higher levels of IL‑10, however lower levels of IL‑2 and IL‑6 compared with the activated control DCs. Together with this pattern of cytokines, 1,25(OH)2D3‑treated DCs exhibited low allogeneic CD4+ T‑cell stimulatory activity and a higher number of CD4+CD25+Foxp3+ cells in the MLR cultures but not in the activated control DCs. These findings indicate that 1,25(OH)2D3 possesses the immunosuppressive properties by upregulating the expression of the inhibitory molecules, HVEM, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases. FAU - Huang, Yi AU - Huang Y AD - Institute of Respiratory Diseases, Xinqiao Hospital, The Third Military Medical University, Chongqing 430037, P.R. China. FAU - Zhao, Yan AU - Zhao Y AD - Department of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 404000, P.R. China. FAU - Ran, Xuemei AU - Ran X AD - Department of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 404000, P.R. China. FAU - Wang, Changzheng AU - Wang C AD - Institute of Respiratory Diseases, Xinqiao Hospital, The Third Military Medical University, Chongqing 430037, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131218 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (CD4 Antigens) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Receptors, Tumor Necrosis Factor, Member 14) RN - 0 (Vitamins) RN - 9006-59-1 (Ovalbumin) RN - FXC9231JVH (Calcitriol) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology MH - CD4 Antigens/metabolism MH - CD4-Positive T-Lymphocytes/immunology/metabolism MH - Calcitriol/*pharmacology MH - Dendritic Cells/cytology/*drug effects/metabolism MH - Down-Regulation/drug effects MH - Female MH - Forkhead Transcription Factors/metabolism MH - Herpesviridae/*metabolism MH - Interleukin-2 Receptor alpha Subunit/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Ovalbumin/pharmacology MH - Receptors, Tumor Necrosis Factor, Member 14/*metabolism MH - T-Lymphocytes, Regulatory/*cytology/immunology/metabolism MH - Up-Regulation/drug effects MH - Vitamins/*pharmacology EDAT- 2013/12/25 06:00 MHDA- 2014/09/25 06:00 CRDT- 2013/12/25 06:00 PHST- 2013/06/17 00:00 [received] PHST- 2013/12/11 00:00 [accepted] PHST- 2013/12/25 06:00 [entrez] PHST- 2013/12/25 06:00 [pubmed] PHST- 2014/09/25 06:00 [medline] AID - 10.3892/mmr.2013.1874 [doi] PST - ppublish SO - Mol Med Rep. 2014 Mar;9(3):813-8. doi: 10.3892/mmr.2013.1874. Epub 2013 Dec 18.