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Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2018 Aug; Vol. 92, pp. 57-66. Date of Electronic Publication: 2018 Jun 13. - Publication Year :
- 2018
-
Abstract
- Objective: Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown. Here, we aimed to establish whether CD11b-ligated moDC modulate Th17 cell effector reponses to assess their potential for future use in moDC-based suppressive immunotherapy.<br />Methods: We generated a bead-based surrogate system to target CD11b on monocyte-derived human dendritic cells and examined the effects of CD11b ligation on Th17-skewing cytokine secretion, priming, expansion and functional plasticity in DC/T cell co-culture systems at the poly- and monoclonal level.<br />Results: We show that Th17 cell expansion within the human memory CD4 <superscript>+</superscript> T cell compartment was efficiently constricted by targeting the CD11b receptor on moDC. This tolerogenic capacity was primarily dependent on cytokine skewing. Furthermore, ligation of CD11b on healthy homozygous carriers of the rs11143679 (ITGAM) variant - a strong genetic susceptibility marker for human systemic lupus erythematosus - also down-modulated the secretion of Th17-skewing cytokines.<br />Conclusion: Overall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Subjects :
- CD18 Antigens metabolism
Cell Differentiation genetics
Cell Plasticity
Cell Proliferation
Cells, Cultured
Coculture Techniques
Cytokines metabolism
Dendritic Cells transplantation
Genetic Predisposition to Disease
Humans
Immune Tolerance
Immunologic Memory
Lupus Erythematosus, Systemic genetics
Lymphocyte Activation
Macrophage-1 Antigen metabolism
Monocytes cytology
Polymorphism, Single Nucleotide
Signal Transduction
Dendritic Cells immunology
Immunotherapy, Adoptive methods
Lupus Erythematosus, Systemic immunology
Macrophage-1 Antigen genetics
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 92
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 29908907
- Full Text :
- https://doi.org/10.1016/j.jaut.2018.05.005