PMID- 37979448
OWN - NLM
STAT- MEDLINE
DCOM- 20231228
LR  - 20240207
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 126
DP  - 2024 Jan 5
TI  - Glyburide-treated human monocyte-derived dendritic cells loaded with insulin 
      represent tolerogenic features with anti-inflammatory responses and modulate 
      autologous T cell responses in vitro.
PG  - 111230
LID - S1567-5769(23)01557-6 [pii]
LID - 10.1016/j.intimp.2023.111230 [doi]
AB  - Tolerogenic dendritic cells (TolDCs) are attractive therapeutic options for 
      autoimmune disorders because they suppress autologous T-cell responses. Dendritic 
      cells (DCs) are equipped with pattern recognition receptors (PRR), including 
      nucleotide-binding and oligomerization domain-like receptors (NLRs) such as 
      NLRP3. Abnormal NLRP3 activation has been reported to be correlated with the 
      occurrence of autoimmune disorders. Accordingly, we hypothesized that glyburide 
      treatment of DCs by blocking the ATP-sensitive K+ (kATP) channels generates 
      TolDCs by inhibiting NLRP3. Insulin was even loaded on a group of 
      glyburide-treated mature DCs (mDCs) to investigate the antigen (Ag) loading 
      effects on glyburide-treated mDCs' phenotypical and functional features. 
      Consequently, T lymphocytes' mediated responses ensuing co-culture of them with 
      control mDCs, insulin loaded and unloaded glyburide treated mDCs were evaluated 
      to determine generated TolDCs' capacity in inhibition of T cell responses that 
      are inducer of destruction in insulin-producing pancreatic beta cells in Type 1 
      Diabetes Mellitus (T1DM). Our findings indicated that glyburide generates 
      desirable TolDCs with decreased surface expression of maturation and Ag 
      presentation related markers and diminished level of inflammatory but increased 
      level of anti-inflammatory cytokines, which even insulin loading demonstrated 
      more anti-inflammatory functions. In addition, co-cultured T cells showed 
      regulatory or T helper 2 phenotype instead of T helper 1 features. Our findings 
      suggested that insulin-loaded and unloaded glyburide-treated DCs are promising 
      therapeutic approaches for autoimmune patients, specifically DCs loaded with 
      insulin for T1DM patients. However, further research is required before this 
      technique can be applied in clinical practice.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Alipour, Shiva
AU  - Alipour S
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 
      Department of Immunology, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Kazemi, Tohid
AU  - Kazemi T
AD  - Department of Immunology, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Sadeghi, Mohammad Reza
AU  - Sadeghi MR
AD  - Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz 
      University of Medical Sciences, Tabriz, Iran.
FAU - Heris, Javad Ahmadian
AU  - Heris JA
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Masoumi, Javad
AU  - Masoumi J
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Naseri, Bahar
AU  - Naseri B
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Baghbani, Elham
AU  - Baghbani E
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
FAU - Sohrabi, Sepideh
AU  - Sohrabi S
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 
      Department of Immunology, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran.
FAU - Baradaran, Behzad
AU  - Baradaran B
AD  - Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 
      Department of Immunology, Faculty of Medicine, Tabriz University of Medical 
      Sciences, Tabriz, Iran. Electronic address: baradaranb@tbzmed.ac.ir.
LA  - eng
PT  - Journal Article
DEP - 20231117
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - SX6K58TVWC (Glyburide)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Insulin)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 1/drug therapy
MH  - Glyburide/pharmacology
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Insulin
MH  - Monocytes
MH  - Immune Tolerance
MH  - *Autoimmune Diseases
MH  - T-Lymphocytes
MH  - Dendritic Cells
OTO - NOTNLM
OT  - Autoimmunity
OT  - Glyburide
OT  - Insulin
OT  - NLRP3
OT  - Tolerogenic Dendritic Cell
OT  - Type 1 diabetes mellitus
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- 2023/11/19 09:42
MHDA- 2023/12/28 06:42
CRDT- 2023/11/18 18:11
PHST- 2023/10/05 00:00 [received]
PHST- 2023/11/10 00:00 [revised]
PHST- 2023/11/11 00:00 [accepted]
PHST- 2023/12/28 06:42 [medline]
PHST- 2023/11/19 09:42 [pubmed]
PHST- 2023/11/18 18:11 [entrez]
AID - S1567-5769(23)01557-6 [pii]
AID - 10.1016/j.intimp.2023.111230 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2024 Jan 5;126:111230. doi: 10.1016/j.intimp.2023.111230. 
      Epub 2023 Nov 17.