PMID- 37176021
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230515
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 9
DP  - 2023 May 5
TI  - Immunosuppressive Polymeric Nanoparticles Targeting Dendritic Cells Alleviate 
      Lupus Disease in Fcgr2b(-/-) Mice by Mediating Antigen-Specific Immune Tolerance.
LID - 10.3390/ijms24098313 [doi]
LID - 8313
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells that have 
      multifaceted functions in the control of immune activation and tolerance. 
      Hyperresponsiveness and altered tolerogenicity of DCs contribute to the 
      development and pathogenesis of system lupus erythematosus (SLE); therefore, 
      DC-targeted therapies aimed at inducing specific immune tolerance have become of 
      great importance for the treatment of SLE. This study developed a new 
      nanoparticle (NP) containing a biodegradable PDMAEMA-PLGA copolymer for 
      target-oriented delivery to DCs in situ. PDMAEMA-PLGA NPs provided sustained drug 
      release and exhibited immunosuppressive activity in FLT3L and GM-CSF-derived bone 
      marrow in conventional DCs (BM-cDCs). PDMAEMA-PLGA NPs improved dexamethasone 
      capability to convert wild-type and Fcgr2b(-/-) BM-cDCs from an immunogenic to 
      tolerogenic state, and BM-cDCs treated with dexamethasone-incorporated 
      PDMAEMA-PLGA NPs (Dex-NPs) efficiently mediated regulatory T cell (Treg) 
      expansion in vitro. Dex-NP therapy potentially alleviated lupus disease in 
      Fcgr2b(-/-) mice by mediating Foxp3(+) Treg expansion in an antigen-specific 
      manner. Our findings substantiate the superior efficacy of DC-targeted therapy 
      using the PDMAEMA-PLGA NP delivery system and provide further support for 
      clinical development as a potential therapy for SLE. Furthermore, PDMAEMA-PLGA NP 
      may be a versatile platform for DC-targeted therapy to induce antigen-specific 
      immune tolerance to unwanted immune responses that occur in autoimmune disease, 
      allergy, and transplant rejection.
FAU - Khiewkamrop, Phuriwat
AU  - Khiewkamrop P
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 
      Thailand.
AD  - Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of 
      Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
AD  - Graduate Program in Medical Microbiology, Graduate School, Chulalongkorn 
      University, Bangkok 10330, Thailand.
FAU - Kaewraemruaen, Chamraj
AU  - Kaewraemruaen C
AUID- ORCID: 0000-0002-1535-9812
AD  - Department of Science and Bioinnovation, Faculty of Liberal Arts and Science, 
      Kasetsart University, Kamphaeng Saen Campus, Nakhon Pathom 73104, Thailand.
FAU - Manipuntee, Chonnavee
AU  - Manipuntee C
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 
      Thailand.
AD  - Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 
      10330, Thailand.
FAU - Saengruengrit, Chalathan
AU  - Saengruengrit C
AD  - Bureau of Quality and Safety of Food, Department of Medical Sciences, Ministry of 
      Public Health, Nonthaburi 11000, Thailand.
FAU - Insin, Numpon
AU  - Insin N
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 
      Thailand.
AD  - Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 
      10330, Thailand.
FAU - Leelahavanichkul, Asada
AU  - Leelahavanichkul A
AD  - Translational Research in Inflammation and Immunology Research Unit (TRIRU), 
      Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 
      Bangkok 10330, Thailand.
FAU - Kaewduangduen, Warerat
AU  - Kaewduangduen W
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 
      Thailand.
FAU - Sonpoung, Opor
AU  - Sonpoung O
AD  - Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, 
      Bangkok 10330, Thailand.
FAU - Ariya-Anandech, Kasirapat
AU  - Ariya-Anandech K
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 
      Thailand.
FAU - Hirankarn, Nattiya
AU  - Hirankarn N
AD  - Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of 
      Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
AD  - Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn 
      University, Bangkok 10330, Thailand.
FAU - Ritprajak, Patcharee
AU  - Ritprajak P
AUID- ORCID: 0000-0003-1392-4061
AD  - Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive 
      Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 
      Thailand.
AD  - Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, 
      Bangkok 10330, Thailand.
LA  - eng
GR  - CU_FRB65_hea (6)_012_32_07/Thailand Science research and Innovation Fund, 
      Chulalongkorn University/
GR  - NA/NSRF via the Program Management Unit for Human Resources & Institutional 
      Development/
GR  - RES_64_141_23_01/Research and Innovation, and the National Research Council of 
      Thailand/
GR  - NA/Second Century Fund (C2F), Chulalongkorn University/
GR  - NA/Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University/
PT  - Journal Article
DEP - 20230505
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (poly(2-(dimethylamino)ethyl methacrylate))
RN  - 0 (Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 0 (Fcgr2b protein, mouse)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Antigens
MH  - Immune Tolerance
MH  - *Lupus Erythematosus, Systemic/therapy
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - Dexamethasone/pharmacology
MH  - Dendritic Cells
MH  - *Nanoparticles
MH  - Receptors, IgG/genetics
PMC - PMC10179670
OTO - NOTNLM
OT  - PDMAEMA-PLGA nanoparticles
OT  - dexamethasone
OT  - immune tolerance
OT  - lupus disease
OT  - tolerogenic dendritic cells
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/13 15:13
MHDA- 2023/05/15 11:42
PMCR- 2023/05/05
CRDT- 2023/05/13 01:30
PHST- 2023/04/07 00:00 [received]
PHST- 2023/04/28 00:00 [revised]
PHST- 2023/05/04 00:00 [accepted]
PHST- 2023/05/15 11:42 [medline]
PHST- 2023/05/13 15:13 [pubmed]
PHST- 2023/05/13 01:30 [entrez]
PHST- 2023/05/05 00:00 [pmc-release]
AID - ijms24098313 [pii]
AID - ijms-24-08313 [pii]
AID - 10.3390/ijms24098313 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 May 5;24(9):8313. doi: 10.3390/ijms24098313.