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Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Apr 07; Vol. 11, pp. 488. Date of Electronic Publication: 2020 Apr 07 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- 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 <superscript>+</superscript> CD11c <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br /> (Copyright © 2020 Santos, Aragão-França, Meira, Cerqueira, Vasconcelos, Nonaka, Pontes-de-Carvalho and Soares.)
- Subjects :
- Animals
Antigen Presentation
Cells, Cultured
Chagas Cardiomyopathy immunology
Chagas Disease immunology
Cytokines metabolism
Dendritic Cells transplantation
Disease Models, Animal
Fibrosis
Humans
Immune Tolerance
Inflammation Mediators metabolism
Mice
Mice, Inbred C57BL
Chagas Cardiomyopathy therapy
Chagas Disease therapy
Dendritic Cells immunology
Immunotherapy, Adoptive methods
Myocardium pathology
T-Lymphocytes, Regulatory immunology
Trypanosoma cruzi physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32318058
- Full Text :
- https://doi.org/10.3389/fimmu.2020.00488