Open AccessMetabolite releasing polymers control dendritic cell function by modulating their energy metabolism
Author(s) -
Joslyn L. Mangal,
Sahil Inamdar,
Yi Yang,
Subhadeep Dutta,
Mamta Wankhede,
Xiaojian Shi,
Haiwei Gu,
Matthew Green,
Kaushal Rege,
Marion Curtis,
Abhinav P. Acharya
Publication year - 2020
Publication title -
journal of materials chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 101
eISSN - 2050-7518
pISSN - 2050-750X
DOI - 10.1039/d0tb00790k
Subject(s) - immune system , microbiology and biotechnology , intracellular , dendritic cell , cd86 , metabolite , glycolysis , biology , immunotherapy , t cell , metabolism , biochemistry , immunology
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.