PMID- 32044665
OWN - NLM
STAT- MEDLINE
DCOM- 20210106
LR  - 20210106
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 81
DP  - 2020 Apr
TI  - Recent discoveries in dendritic cell tolerance-inducing pharmacological 
      molecules.
PG  - 106275
LID - S1567-5769(19)32616-5 [pii]
LID - 10.1016/j.intimp.2020.106275 [doi]
AB  - Dendritic cells (DCs) represent one of the most important biological tools for 
      cellular immunotherapy purposes. There are an increasing number of phase I and II 
      studies, where regulatory or tolerogenic DCs (TolDCs) are utilized as negative 
      vaccines, with the aim of inducing tolerogenic outcomes in patients with various 
      autoimmune or chronic-inflammatory diseases, as well as in transplant settings. 
      The induction of tolerogenic properties in DCs can be achieved by altering their 
      activation state toward expression of immunosuppressive elements and/or by 
      achieving resistance to maturation, which leads to insufficient co-stimulatory 
      signal delivery and inability to efficiently present antigens. In the past, one 
      of the most efficient ways to induce DC tolerance has been the application of 
      selected pharmacological agents which actively induce a tolerogenic transcription 
      program or inhibit major pro-inflammatory transcription factors such as Nf-kappaB. 
      Important examples include immunosuppressants such as different corticosteroids, 
      vitamin D(3), rapamycin and others. The quality of TolDCs induced by different 
      approaches is becoming a vital issue and recent evidence suggests substantial 
      heterogeneity between variously-generated TolDCs as evidenced by their 
      transcriptomic profile and function. The possibility of various "flavors" of 
      TolDCs encourages future research in discovery of Tol-DC inducing agents to 
      enrich various ways of DC manipulation. This would enable a broader range of 
      tools to manipulate DC toward specific characteristics desirable in different 
      disease settings. In recent years, several novel small molecules have been 
      identified with the capacity to promote DC tolerogenic characteristics. In this 
      review, we will present and discuss these novel findings and also highlight novel 
      understandings of tolerogenic mechanisms by which DC tolerogenicity is induced by 
      already established agents.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Svajger, Urban
AU  - Svajger U
AD  - Blood Transfusion Center of Slovenia, Slajmerjeva 6, 1000 Ljubljana, Slovenia. 
      Electronic address: urban.svajger@ztm.si.
FAU - Rozman, Primoz J
AU  - Rozman PJ
AD  - Blood Transfusion Center of Slovenia, Slajmerjeva 6, 1000 Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200207
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Cell Differentiation
MH  - Dendritic Cells/*immunology
MH  - Drug Discovery
MH  - Drug Therapy/*methods
MH  - Humans
MH  - Immune Tolerance/*drug effects
MH  - Immunotherapy/*methods
MH  - T-Lymphocytes, Regulatory/*immunology
OTO - NOTNLM
OT  - Dendritic cells
OT  - Drugs
OT  - Molecules
OT  - Pharmacological
OT  - Tolerance
OT  - Tolerogenic
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/02/12 06:00
MHDA- 2021/01/07 06:00
CRDT- 2020/02/12 06:00
PHST- 2019/11/15 00:00 [received]
PHST- 2020/01/31 00:00 [revised]
PHST- 2020/01/31 00:00 [accepted]
PHST- 2020/02/12 06:00 [pubmed]
PHST- 2021/01/07 06:00 [medline]
PHST- 2020/02/12 06:00 [entrez]
AID - S1567-5769(19)32616-5 [pii]
AID - 10.1016/j.intimp.2020.106275 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2020 Apr;81:106275. doi: 10.1016/j.intimp.2020.106275. Epub 
      2020 Feb 7.