DEXterity of tolerogenic <scp>APC</scp>s

Stagliano, Katherine E.; Oppenheim, Joost J.

doi:10.1002/eji.201243184

Cited by 3 publications

(3 citation statements)

References 25 publications

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“…DCs have the ability to activate or induce T cell tolerance ( Stagliano and Oppenheim, 2013 ), as determined by their state of maturation ( Jansen et al., 2017 ). When mature DCs mediate immune responses in inflammatory conditions, these cells have a regulatory profile with the ability to induce immune tolerance, oppositely to DCs expressing an immature phenotype ( Domogalla et al., 2017 ; Moreau et al., 2017 ).…”

Section: Immunomodulatory Agents and CCCmentioning

confidence: 99%

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Santos

Silva

Reis

et al. 2021

Front. Cell. Infect. Microbiol.

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Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

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Section: Immunomodulatory Agents and CCCmentioning

confidence: 99%

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Santos

Silva

Reis

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Alternative treatments are needed, with the aim of reducing morbidity and mortality, and providing a better quality of life for the patients with CCC. Therapeutic alternatives focused on reducing the immunological mechanisms, which are key factors in the pathogenesis of the disease, modulating both inflammation and fibrosis in the heart of the patients, are of great interest (10)(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

“…In this context, immunotherapy with dendritic cells (DCs) appears as an option for the development of treatments based on their role in immune responses. Dendritic cells are APCs which can activate T cells and induce T cell tolerance (15). They are important as mediators for the induction of effective immunity against invading pathogens, by connection of innate and adaptive immune responses and maintenance of immune tolerance (17,18).…”

Section: Introductionmentioning

confidence: 99%

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease

et al. 2020

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Chronic Chagas disease cardiomyopathy (CCC) is the most frequent and severe form of this parasitic disease. CCC is caused by a progressive inflammation in the heart, resulting in alterations that can culminate in heart failure and death. The use of dendritic cells (DCs) appears as an option for the development of treatments due to their important role in regulating immune responses. Here, we investigated whether tolerogenic cells (tDCs) could interfere with the progression of CCC in an experimental model of Chagas disease. The tDCs were generated and characterized as CD11b + CD11c + cells, low expression of MHC-II, CD86, CD80, and CD40, and increased expression of PD-L. These cells produced low levels of IL-6 and IL-12p70 and higher levels of IL-10, compared to mature DCs (mDCs). Interestingly, tDCs inhibited lymphoproliferation and markedly increased the population of FoxP3 + Treg cells in vitro, compared to mature DCs. In a mouse model of CCC, treatment with tDCs reduced heart inflammation and fibrosis. Furthermore, tDCs treatment reduced the gene expression of pro-inflammatory cytokines (Ifng and Il12) and of genes related to cardiac remodeling (Col1a2 and Lgals3), while increasing the gene expression of IL-10. Finally, administration of tDCs, increased the percentage of Treg cells in the hearts and spleens of chagasic mice. Ours results show that tolerogenic dendritic cells have therapeutic potential on CCC, inhibiting disease progression.

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Complete Tolerogenic Adjuvant Stimulates Regulatory T Cell Response to Immunization

Zheng

Geng

Yan

et al. 2023

The Journal of Immunology

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We have determined in mice the minimum composition required for forming a vaccine adjuvant that stimulates a regulatory T (Treg) cell response to immunization, and we named the adjuvant “complete tolerogenic adjuvant.” This new kind of adjuvant may let us use the well-proven “Ag with adjuvant” form of immunization for inducing Treg cell–mediated Ag-specific immunosuppression. The minimum composition consists of dexamethasone, rapamycin, and monophosphoryl lipid A at a mass ratio of 8:20:3. By dissecting the respective role of each of these components during immunization, we have further shown why immunosuppressive and immunogenic agents are both needed for forming true adjuvants for Treg cells. This finding may guide the design of additional, and potentially more potent, complete tolerogenic adjuvants with which we may form numerous novel vaccines for treating immune diseases.

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DEXterity of tolerogenic APCs

Cited by 3 publications

References 25 publications

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease

Complete Tolerogenic Adjuvant Stimulates Regulatory T Cell Response to Immunization

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