HMGN1 and R848 Synergistically Activate Dendritic Cells Using Multiple Signaling Pathways

Alam, Masud; Yang, De; Trivett, Anna; Meyer, Thomas J.; Oppenheim, Joost J.

doi:10.3389/fimmu.2018.02982

Cited by 32 publications

(30 citation statements)

References 53 publications

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“…Absence of tumor specific immune response in Hmgn1 −/− mice and increased anti-tumor immune response, when vaccinated mice with DNA vector overexpressing HMGN1, provide further support the role of HMGN proteins in regulating immune cell function and response [88]. Intratumor delivery of HMGN1 and TLT7/8 synthetic agonist R848, along with a checkpoint inhibitor Cytoxan synergistically activates dendritic cells for optimal Th1 response and eradicated large established CT26 tumors in mice [89,90]. Moreover, low doses of HMGN1 with anti-CD4 depleting antibody promoted the expansion of anti-tumor CD8 T cells by rescuing them from exhaustion [91].…”

Section: Immune Functionsmentioning

confidence: 78%

Biological Functions of HMGN Chromosomal Proteins

Nanduri

Furusawa

Bustin

2020

IJMS

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Chromatin plays a key role in regulating gene expression programs necessary for the orderly progress of development and for preventing changes in cell identity that can lead to disease. The high mobility group N (HMGN) is a family of nucleosome binding proteins that preferentially binds to chromatin regulatory sites including enhancers and promoters. HMGN proteins are ubiquitously expressed in all vertebrate cells potentially affecting chromatin function and epigenetic regulation in multiple cell types. Here, we review studies aimed at elucidating the biological function of HMGN proteins, focusing on their possible role in vertebrate development and the etiology of disease. The data indicate that changes in HMGN levels lead to cell type-specific phenotypes, suggesting that HMGN optimize epigenetic processes necessary for maintaining cell identity and for proper execution of specific cellular functions. This manuscript contains tables that can be used as a comprehensive resource for all the English written manuscripts describing research aimed at elucidating the biological function of the HMGN protein family.

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Section: Immune Functionsmentioning

confidence: 78%

Biological Functions of HMGN Chromosomal Proteins

Nanduri

Furusawa

Bustin

2020

IJMS

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“…In fact, the abundance of infiltrating leukocytes is an independent risk factor for the pathologic progression of acute myocarditis into long-term cardiac dysfunction [ 30 ]. The majority of the accumulated leukocytes in inflamed heart tissue of CV-infected mice are CD11b + monocytes and macrophages [ 35 , 40 ], with infiltration of these immune cells being driven by respective chemotactic cytokines [ 2 ]. Others and we demonstrated that particularly those infiltrating myeloid cells contribute to acute and chronic functional impairment in inflammatory heart disease [ 24 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Mitigated viral myocarditis in A/J mice by the immunoproteasome inhibitor ONX 0914 depends on inhibition of systemic inflammatory responses in CoxsackievirusB3 infection

et al. 2021

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A preclinical model of troponin I-induced myocarditis (AM) revealed a prominent role of the immunoproteasome (ip), the main immune cell-resident proteasome isoform, in heart-directed autoimmunity. Viral infection of the heart is a known trigger of cardiac autoimmunity, with the ip enhancing systemic inflammatory responses after infection with a cardiotropic coxsackievirusB3 (CV). Here, we used ip-deficient A/J-LMP7−/− mice to investigate the role of ip-mediated effects on adaptive immunity in CV-triggered myocarditis and found no alteration of the inflammatory heart tissue damage or cardiac function in comparison to wild-type controls. Aiming to define the impact of the systemic inflammatory storm under the control of ip proteolysis during CV infection, we targeted the ip in A/J mice with the inhibitor ONX 0914 after the first cycle of infection, when systemic inflammation has set in, well before cardiac inflammation. During established acute myocarditis, the ONX 0914 treatment group had the same reduction in cardiac output as the controls, with inflammatory responses in heart tissue being unaffected by the compound. Based on these findings and with regard to the known anti-inflammatory role of ONX 0914 in CV infection, we conclude that the efficacy of ip inhibitors for CV-triggered myocarditis in A/J mice relies on their immunomodulatory effects on the systemic inflammatory reaction.

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“…Multiple studies from Dr. Oppenheim's group have shown how HMGN1 contributes to the generation of antitumor immunity and has therefore drawn interest as a potential target for antitumor therapy (71). They made the observation that synergistic effect of R848 (TLR7/8 agonist) along with HMGN1 (TLR4 agonist) leads to augmented IL-12 responses and phenotypic maturation of mouse bone marrow derived dendritic cells (BMDCs) (72). This led to the development of a therapeutic vaccine (TheraVac) combining HMGN1 and R848 plus a checkpoint inhibitor (Cytoxan), which is effective on large tumors in mice without use of exogenous tumor-associated antigen(s) (73).…”

Section: Vaccines For Non-infectious Indicationsmentioning

confidence: 99%

Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference

et al. 2020

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Other than clean drinking water, vaccines have been the most effective public health intervention in human history, yet their full potential is still untapped. To date, vaccine development has been largely limited to empirical approaches focused on infectious diseases and has targeted entire populations, potentially disregarding distinct immunity in vulnerable populations such as infants, elders, and the immunocompromised. Over the past few decades innovations in genetic engineering, adjuvant discovery, formulation science, and systems biology have fueled rapid advances in vaccine research poised to consider demographic factors (e.g., age, sex, genetics, and epigenetics) in vaccine discovery and development. Current efforts are focused on leveraging novel approaches to vaccine discovery and development to optimize vaccinal antigen and, as needed, adjuvant systems to enhance vaccine immunogenicity while maintaining safety. These approaches are ushering in an era of precision vaccinology aimed at tailoring immunization for vulnerable populations with distinct immunity. To foster collaboration among leading vaccinologists, government, policy makers, industry partners, and funders from around the world, the Precision Vaccines Program at Boston Children's Hospital hosted the 2 nd International Precision Vaccines Conference (IPVC) at Harvard Medical School on the 17 th-18 th October 2019. The conference convened experts in vaccinology, including vaccine formulation and adjuvantation, immunology, cell signaling, systems biology, biostatistics, bioinformatics, as well as vaccines for non-infectious indications such as cancer and opioid use disorder. Herein we review highlights from the 2 nd IPVC and discuss key concepts in the field of precision vaccines.

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HMGN1 and R848 Synergistically Activate Dendritic Cells Using Multiple Signaling Pathways

Cited by 32 publications

References 53 publications

Biological Functions of HMGN Chromosomal Proteins

Biological Functions of HMGN Chromosomal Proteins

Mitigated viral myocarditis in A/J mice by the immunoproteasome inhibitor ONX 0914 depends on inhibition of systemic inflammatory responses in CoxsackievirusB3 infection

Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference

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