PMID- 33647585
OWN - NLM
STAT- MEDLINE
DCOM- 20220118
LR  - 20240226
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 142
DP  - 2021 Jun
TI  - The murine DCs transfected with DNA-plasmid encoding CCR9 demonstrate the 
      increased migration to CCL25 and thymic cells in vitro and to the thymus in vivo.
PG  - 155473
LID - S1043-4666(21)00053-3 [pii]
LID - 10.1016/j.cyto.2021.155473 [doi]
AB  - BACKGROUND: B220(+)CD11c(+)plasmacytoid DCs(pDCs) are known to participate in the 
      negative selection and central tolerance induction by the capturing of 
      self-antigens in peripheral tissues and further migration to the thymus using the 
      CCL25-CCR9 chemotaxis axis. AIM: Here we investigate the possibility of DCs 
      migration stimulation to the thymus by the transfection with plasmid 
      DNA-constructs encoding CCR9(pmaxCCR9) to develop a system for desired antigen 
      delivery to the thymus for central tolerance induction. METHODS: Dendritic 
      cells(DCs) cultures were generated from UBC-GFP mice bone marrow cells expressing 
      green fluorescent protein using the rmFlt3-L. DCs cultures were transfected with 
      pmaxCCR9 by electroporation. The efficiency of electroporation was confirmed by 
      RT-qPCR and flow cytometry. The migration of electroporated DCs was assessed in 
      vitro and in vivo. RESULTS: Dendritic cells(DCs) cultures obtained from UBC-GFP 
      mice contained both B220(+)pDCs and SIRPa(+)cDC2. According to the RT-qPCR assay, 
      the electroporation of obtained DCs cultures with pmaxCCR9 resulted in a 
      94.4-fold increase of RNA encoding CCR9 compared with non-electroporated 
      cultures. Flow cytometry data showed that DCs cultures electroporated with 
      pmaxCCR9 contained a significantly higher frequency of DCs carrying significantly 
      higher levels of surface CCR9. Migration dynamics of obtained DCs analyzed in 
      vitro showed that pmaxCCR9 electroporated DCs migrated significantly more active 
      to CCL25 and thymic cells than non-electroporated and mock-electroporated DCs. In 
      vivo, 30 days after injection, the relative amount of the DCs electroporated with 
      pmaxCCR9 and pmaxMHC encoding antigenic determinants in the mice thymuses was 
      2.02-fold higher than the relative amount of the DCs electroporated with control 
      plasmid. CONCLUSION: Thus, the electroporation of murine DCs with pmaxCCR9 
      stimulated its migration to CCL25 and thymic cells in vitro as well as to the 
      thymus in vivo. The obtained DCs loaded with a desired antigen may be suggested 
      for further evaluation of central tolerance induction ability in in vivo models 
      of autoimmune diseases and transplantation.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Tereshchenko, Valeriy
AU  - Tereshchenko V
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia.
FAU - Bulygin, Aleksei
AU  - Bulygin A
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia.
FAU - Zavodskii, Roman
AU  - Zavodskii R
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia.
FAU - Maksyutov, Amir
AU  - Maksyutov A
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia; State Research Center of Virology and Biotechnology "Vector", 630559 
      Koltsovo, Russia.
FAU - Kurilin, Vasiliy
AU  - Kurilin V
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia.
FAU - Fisher, Marina
AU  - Fisher M
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia.
FAU - Semenyuk, Nikita
AU  - Semenyuk N
AD  - Novosibirsk State University, 630090 Novosibirsk, Russia.
FAU - Aladev, Stanislav
AU  - Aladev S
AD  - Novosibirsk State University, 630090 Novosibirsk, Russia.
FAU - Sennikov, Sergey
AU  - Sennikov S
AD  - Research Institute of Fundamental and Clinical Immunology, 630099 Novosibirsk, 
      Russia; Novosibirsk State University, 630090 Novosibirsk, Russia. Electronic 
      address: sennikovsv@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210226
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Antigens)
RN  - 0 (CC chemokine receptor 9)
RN  - 0 (Ccl25 protein, mouse)
RN  - 0 (Chemokines, CC)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, CCR)
RN  - 0 (flt3 ligand protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Antigens/metabolism
MH  - *Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokines, CC/*metabolism
MH  - DNA/*metabolism
MH  - Dendritic Cells/cytology/drug effects/*metabolism
MH  - Electroporation
MH  - Green Fluorescent Proteins/metabolism
MH  - Male
MH  - Membrane Proteins/pharmacology
MH  - Mice, Inbred C57BL
MH  - Plasmids/*metabolism
MH  - Receptors, CCR/*metabolism
MH  - Thymus Gland/*cytology
MH  - *Transfection
MH  - Transgenes
MH  - Mice
OTO - NOTNLM
OT  - CCL25
OT  - CCR9
OT  - Migration
OT  - Thymus
OT  - conventional DC type 2
OT  - plasmacytoid DCs
EDAT- 2021/03/02 06:00
MHDA- 2022/01/19 06:00
CRDT- 2021/03/01 20:14
PHST- 2020/11/20 00:00 [received]
PHST- 2021/02/09 00:00 [revised]
PHST- 2021/02/09 00:00 [accepted]
PHST- 2021/03/02 06:00 [pubmed]
PHST- 2022/01/19 06:00 [medline]
PHST- 2021/03/01 20:14 [entrez]
AID - S1043-4666(21)00053-3 [pii]
AID - 10.1016/j.cyto.2021.155473 [doi]
PST - ppublish
SO  - Cytokine. 2021 Jun;142:155473. doi: 10.1016/j.cyto.2021.155473. Epub 2021 Feb 26.