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

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

doi:10.1039/d0tb00790k

Cited by 25 publications

(16 citation statements)

References 39 publications

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“…Larp1 is an RNA-binding protein that functions downstream of mTORC1 to regulate the translation of 59-terminal oligopyrimidine tract (TOP) mRNAs, such as those encoding ribosome proteins (4244). Consistent with the effects of exogenous IL-10 reducing glycolysis, Mangal et al (45) recently reported the effects of exogenous a-ketoglutarate polymeric microparticles on cell metabolism in BMDCs. The authors reported that exogenous a-ketoglutarate microparticles significantly decreased glycolysis and mitochondrial respiration but did not affect MHC-II and CD86 expression.…”

Section: Discussionmentioning

confidence: 64%

Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function

Cruz

Giri

Turro

et al. 2021

The Journal of Immunology

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Deficiency of lymphocyte activation gene-3 (LAG3) is significantly associated with increased cardiovascular disease risk with in vitro results demonstrating increased TNF-α and decreased IL-10 secretion from LAG3-deficient human B lymphoblasts. The hypothesis tested in this study was that Lag3 deficiency in dendritic cells (DCs) would significantly affect cytokine expression, alter cellular metabolism, and prime naive T cells to greater effector differentiation. Experimental approaches used included differentiation of murine bone marrow–derived DCs (BMDCs) to measure secreted cytokines, cellular metabolism, RNA sequencing, whole cell proteomics, adoptive OT-II CD4+Lag3+/+ donor cells into wild-type (WT) C57BL/6 and Lag3−/− recipient mice, and ex vivo measurements of IFN-γ from cultured splenocytes. Results showed that Lag3−/− BMDCs secreted more TNF-α, were more glycolytic, used fewer fatty acids for mitochondrial respiration, and glycolysis was significantly reduced by exogenous IL-10 treatment. Under basal conditions, RNA sequencing revealed increased expression of CD40 and CD86 and other cytokine-signaling targets as compared with WT. Whole cell proteomics identified a significant number of proteins up- and downregulated in Lag3−/− BMDCs, with significant differences noted in exogenous IL-10 responsiveness compared with WT cells. Ex vivo, IFN-γ expression was significantly higher in Lag3−/− mice as compared with WT. With in vivo adoptive T cell and in vitro BMDC:T coculture experiments, Lag3−/− BMDCs showed greater T cell effector differentiation and proliferation, respectively, compared with WT BMDCs. In conclusion, Lag3 deficiency in DCs is associated with an inflammatory phenotype that provides a plausible mechanism for increased cardiovascular disease risk in humans with LAG3 deficiency.

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Section: Discussionmentioning

confidence: 64%

Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function

Cruz

Giri

Turro

et al. 2021

The Journal of Immunology

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“…In addition to development of vaccines, engineering the immune system also involves mimicking cellular and molecular mechanisms present in the immune system. For example, biomaterials can be utilized to mimic immune cells by delivering proteins and small molecules [ 188–193 ] and affect the overall outcome of the disease. Moreover, immune engineering also involves delivery of cells shielded from the immune system for affecting the outcome of different diseases and disorders.…”

Section: Future Outlook: Application Of Cofs In Immune Engineeringmentioning

confidence: 99%

Covalent Organic Frameworks for Biomedical Applications

Esrafili

Wagner

Inamdar

et al. 2021

Adv Healthcare Materials

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112

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Covalent organic frameworks (COFs) are porous organic polymeric materials that are composed of organic elements and linked together by the thermodynamically stable covalent bonds. The applications of COFs in energy sector and drug delivery are afforded because of the desirable properties of COFs, such as high stability, low density, large surface area, multidimensionality, porosity, and high‐ordered crystalline structure expanded. In this review COFs are reviewed, from the perspective of different types of reported COFs, different methods for their synthesis, and their potential applications in the biomedical field. The main goal of this review is to introduce COFs as a biomaterial and to identify specific advantages of different types of COFs that can be exploited for specialized biomedical applications, such as immune engineering.

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“…The paKG polymer was formulated using previously described techniques. 8,16 Briefly, an equimolar ratio of alpha-ketoglutarate and 1,10-decanediol were placed under a vacuum in a round bottom flask and was continuously stirred for 2 h at 130 °C. Methanol was used to precipitate the generated polymer.…”

Section: Polymer Synthesismentioning

confidence: 99%

Short term, low dose alpha-ketoglutarate based polymeric nanoparticles with methotrexate reverse rheumatoid arthritis symptoms in mice and modulate T helper cell responses

et al. 2022

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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 modulate the function of the immune cells.

Cited by 25 publications

References 39 publications

Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function

Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function

Covalent Organic Frameworks for Biomedical Applications

Short term, low dose alpha-ketoglutarate based polymeric nanoparticles with methotrexate reverse rheumatoid arthritis symptoms in mice and modulate T helper cell responses

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