PMID- 37511064
OWN - NLM
STAT- MEDLINE
DCOM- 20230731
LR  - 20230731
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 14
DP  - 2023 Jul 11
TI  - Engineered Human Dendritic Cell Exosomes as Effective Delivery System for Immune 
      Modulation.
LID - 10.3390/ijms241411306 [doi]
LID - 11306
AB  - Exosomes (exos) contain molecular cargo of therapeutic and diagnostic value for 
      cancers and other inflammatory diseases, but their therapeutic potential for 
      periodontitis (PD) remains unclear. Dendritic cells (DCs) are the directors of 
      immune response and have been extensively used in immune therapy. We previously 
      reported in a mouse model of PD that custom murine DC-derived exo subtypes could 
      reprogram the immune response toward a bone-sparing or bone-loss phenotype, 
      depending on immune profile. Further advancement of this technology requires the 
      testing of human DC-based exos with human target cells. Our main objective in 
      this study is to test the hypothesis that human monocyte-derived dendritic cell 
      (MoDC)-derived exos constitute a well-tolerated and effective immune therapeutic 
      approach to modulate human target DC and T cell immune responses in vitro. MoDC 
      subtypes were generated with TGFb/IL-10 (regulatory (reg) MoDCs, 
      CD86(low)HLA-DR(low)PDL1(high)), E. coli LPS (stimulatory (stim) MoDCs, 
      CD86(high)HLA-DR(high)PDL1(low)) and buffer (immature (i) MoDCs, 
      CD86(low)HLA-DR(med)PDL1(low)). Exosomes were isolated from different MoDC 
      subtypes and characterized. Once released from the secreting cell into the 
      surrounding environment, exosomes protect their prepackaged molecular cargo and 
      deliver it to bystander cells. This modulates the functions of these cells, 
      depending on the cargo content. RegMoDCexos were internalized by recipient MoDCs 
      and induced upregulation of PDL1 and downregulation of costimulatory molecules 
      CD86, HLADR, and CD80, while stimMoDCexos had the opposite influence. RegMoDCexos 
      induced CD25+Foxp3+ Tregs, which expressed CTLA4 and PD1 but not IL-17A. In 
      contrast, T cells treated with stimMoDCexos induced IL-17A+ Th17 T cells, which 
      were negative for immunoregulatory CTLA4 and PD1. T cells and DCs treated with 
      iMoDCexos were immune 'neutral', equivalent to controls. In conclusion, human DC 
      exos present an effective delivery system to modulate human DC and T cell immune 
      responses in vitro. Thus, MoDC exos may present a viable immunotherapeutic agent 
      for modulating immune response in the gingival tissue to inhibit bone loss in 
      periodontal disease.
FAU - Elsayed, Ranya
AU  - Elsayed R
AD  - Department of Periodontics, Dental College of Georgia, Augusta University, 
      Augusta, GA 30912, USA.
FAU - Elashiry, Mahmoud
AU  - Elashiry M
AD  - Department of Periodontics, Dental College of Georgia, Augusta University, 
      Augusta, GA 30912, USA.
FAU - Tran, Cathy
AU  - Tran C
AD  - Department of Periodontics, Dental College of Georgia, Augusta University, 
      Augusta, GA 30912, USA.
FAU - Yang, Tigerwin
AU  - Yang T
AD  - Department of Periodontics, Dental College of Georgia, Augusta University, 
      Augusta, GA 30912, USA.
FAU - Carroll, Angelica
AU  - Carroll A
AD  - Department of Periodontics, Dental College of Georgia, Augusta University, 
      Augusta, GA 30912, USA.
FAU - Liu, Yutao
AU  - Liu Y
AUID- ORCID: 0000-0003-2870-4504
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 
      University, Augusta, GA 30912, USA.
FAU - Hamrick, Mark
AU  - Hamrick M
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 
      University, Augusta, GA 30912, USA.
FAU - Cutler, Christopher W
AU  - Cutler CW
AD  - Department of Periodontics, Dental College of Georgia, Augusta University, 
      Augusta, GA 30912, USA.
LA  - eng
GR  - NIH/NIDCR R01 DE14328/NIH/NIDCR/
PT  - Journal Article
DEP - 20230711
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - CTLA-4 Antigen
MH  - *Exosomes
MH  - Escherichia coli
MH  - Dendritic Cells
MH  - HLA-DR Antigens
MH  - Immunity
MH  - Cell Differentiation
MH  - Monocytes
PMC - PMC10379002
OTO - NOTNLM
OT  - dendritic cells
OT  - exosomes
OT  - immunotherapy
OT  - periodontitis
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/29 11:48
MHDA- 2023/07/31 06:42
PMCR- 2023/07/11
CRDT- 2023/07/29 01:21
PHST- 2023/03/24 00:00 [received]
PHST- 2023/06/27 00:00 [revised]
PHST- 2023/06/28 00:00 [accepted]
PHST- 2023/07/31 06:42 [medline]
PHST- 2023/07/29 11:48 [pubmed]
PHST- 2023/07/29 01:21 [entrez]
PHST- 2023/07/11 00:00 [pmc-release]
AID - ijms241411306 [pii]
AID - ijms-24-11306 [pii]
AID - 10.3390/ijms241411306 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jul 11;24(14):11306. doi: 10.3390/ijms241411306.