Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

Joslyn L. Mangal; Sahil Inamdar; Yi Yang; Subhadeep Dutta; Mamta Wankhede; Xiaojian Shi; Haiwei Gu; Matthew Green; Kaushal Rege; Marion Curtis; Abhinav P. Acharya

doi:10.1039/d0tb00790k

Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

Joslyn L. Mangal, Sahil Inamdar, Yi Yang, Subhadeep Dutta, Mamta Wankhede, Xiaojian Shi, Haiwei Gu, Matthew Green, Kaushal Rege, Marion Curtis, Abhinav P. Acharya

Allergy, Asthma and Clinical Immunology

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro. These metabolic changes resulted in modulation of MHC-II, CD86 expression in DCs, and altered the frequency of regulatory T cells (Tregs), and T-helper type-1/2/17 cells in vitro. This unique strategy of intracellular delivery of key-metabolites in a sustained manner provides a new direction in immunometabolism field-based immunotherapy with potential applications in different diseases associated with immune disorders.

Original language	English (US)
Pages (from-to)	5195-5203
Number of pages	9
Journal	Journal of Materials Chemistry B
Volume	8
Issue number	24
DOIs	https://doi.org/10.1039/d0tb00790k
State	Published - Jun 28 2020

ASJC Scopus subject areas

General Chemistry
Biomedical Engineering
General Materials Science

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title = "Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism",

abstract = "Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro. These metabolic changes resulted in modulation of MHC-II, CD86 expression in DCs, and altered the frequency of regulatory T cells (Tregs), and T-helper type-1/2/17 cells in vitro. This unique strategy of intracellular delivery of key-metabolites in a sustained manner provides a new direction in immunometabolism field-based immunotherapy with potential applications in different diseases associated with immune disorders.",

author = "Mangal, {Joslyn L.} and Sahil Inamdar and Yi Yang and Subhadeep Dutta and Mamta Wankhede and Xiaojian Shi and Haiwei Gu and Matthew Green and Kaushal Rege and Marion Curtis and Acharya, {Abhinav P.}",

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month = jun,

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doi = "10.1039/d0tb00790k",

language = "English (US)",

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T1 - Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

AU - Mangal, Joslyn L.

AU - Inamdar, Sahil

AU - Yang, Yi

AU - Dutta, Subhadeep

AU - Wankhede, Mamta

AU - Shi, Xiaojian

AU - Gu, Haiwei

AU - Green, Matthew

AU - Rege, Kaushal

AU - Curtis, Marion

AU - Acharya, Abhinav P.

PY - 2020/6/28

Y1 - 2020/6/28

N2 - Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro. These metabolic changes resulted in modulation of MHC-II, CD86 expression in DCs, and altered the frequency of regulatory T cells (Tregs), and T-helper type-1/2/17 cells in vitro. This unique strategy of intracellular delivery of key-metabolites in a sustained manner provides a new direction in immunometabolism field-based immunotherapy with potential applications in different diseases associated with immune disorders.

AB - Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro. These metabolic changes resulted in modulation of MHC-II, CD86 expression in DCs, and altered the frequency of regulatory T cells (Tregs), and T-helper type-1/2/17 cells in vitro. This unique strategy of intracellular delivery of key-metabolites in a sustained manner provides a new direction in immunometabolism field-based immunotherapy with potential applications in different diseases associated with immune disorders.

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EP - 5203

JO - Journal of Materials Chemistry B

JF - Journal of Materials Chemistry B

IS - 24

ER -

Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

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