Edited by: Angela Haczku
Regulatory dendritic cell expression of MHCII and IL-10 are jointly requisite for induction of tolerance in a murine model of OVA-asthma
Article first published online: 2 AUG 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 68, Issue 9, pages 1126–1135, September 2013
How to Cite
Regulatory dendritic cell expression of MHCII and IL-10 are jointly requisite for induction of tolerance in a murine model of OVA-asthma. Allergy 2013; 68: 1126–1135., , , , , .
- Issue published online: 18 SEP 2013
- Article first published online: 2 AUG 2013
- Manuscript Accepted: 6 MAY 2013
- Canadian Institutes of Health Research. Grant Number: MOP-53167
- MHCII ;
- tolerogenic dendritic cells
Allergen-presenting dendritic cells differentiated with IL-10 (DC10) reverse the asthma phenotype in mice by converting their Th2 cells to regulatory T cells (Tregs). DC10 express elevated levels of IL-10, but substantially reduced levels of MHCII and costimulatory molecules, so the relationships between these factors with each other and tolerogenicity have not been clearly elucidated.
We assessed the roles of these inputs in DC10 reversal of OVA-associated asthma-like disease by treating affected mice with OVA-pulsed DC10 generated from wild-type or IL-10-sufficient MHCII−/− or CD80/CD86−/− mice, or with MHCII-intact IL-10-silenced DC10.
IL-10 silencing did not discernibly affect the cells' immunobiology (e.g., costimulatory molecules, chemokines), but it eliminated IL-10 secretion and the cell's abilities to induce tolerance, as determined by assessments of airway hyper-responsiveness, eosinophilia, and Th2 responses to recall OVA challenge. MHCII−/− DC10 expressed normal levels of IL-10, but, nevertheless, were unable to induce allergen tolerance in asthma phenotype mice, while tolerance induced by CD80/CD86−/− DC10 was attenuated but not eliminated. We also assessed the induction of multiple Treg cell markers (e.g., ICOS, PD-1, GITR) on pulmonary CD25+Foxp3+ cells in the treated mice. Wild-type DC10 treatments upregulated expression of each marker, while neither IL-10-silenced nor MHCII−/− DC10 did so, and the CD80/86−/− DC10 induced an intermediate Treg cell activation phenotype.
Both IL-10 and MCHII expression by DC10 are requisite, but not sufficient for tolerance induction, suggesting that DC10 and Th2 effector T cells must be brought together in a cognate fashion in order for their IL-10 to induce tolerance.