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AIRE is not essential for the induction of human tolerogenic dendritic cells.
- Source :
-
Autoimmunity . Jun2016, Vol. 49 Issue 4, p211-218. 8p. - Publication Year :
- 2016
-
Abstract
- Loss-of-function mutations of the Autoimmune Regulator (AIRE) gene results in organ-specific autoimmunity and disease Autoimmune Polyendocrinopathy type 1 (APS1)/Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED). The AIRE protein is crucial in the induction of central tolerance, promoting ectopic expression of tissue-specific antigens in medullary thymic epithelial cells and enabling removal of self-reactive T-cells. AIRE expression has recently been detected in myeloid dendritic cells (DC), suggesting AIRE may have a significant role in peripheral tolerance. DC stimulation of T-cells is critical in determining the initiation or lack of an immune response, depending on the pattern of costimulation and cytokine production by DCs, defining immunogenic/inflammatory (inflDC) and tolerogenic (tolDC) DC. In AIRE-deficient patients and healthy controls, we validated the role ofAIREin the generation and function of monocyte-derived inflDC and tolDCs by determining mRNA and protein expression of AIRE and comparing activation markers (HLA-DR/DP/DQ,CD83,CD86,CD274(PDL-1),TLR-2), cytokine production (IL-12p70,IL-10,IL-6,TNF-α,IFN-γ) and T-cell stimulatory capacity (mixed lymphocyte reaction) of AIRE+ and AIRE- DCs. We show for the first time that: (1) tolDCs from healthy individuals express AIRE; (2) AIRE expression is not significantly higher in tolDC compared to inflDC; (3) tolDC can be generated from APECED patient monocytes and (4) tolDCs lacking AIRE retain the same phenotype and reduced T-cell stimulatory function. Our findings suggest that AIRE does not have a role in the induction and function of monocyte-derived tolerogenic DC in humans, but these findings do not exclude a role for AIRE in peripheral tolerance mediated by other cell types. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 08916934
- Volume :
- 49
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 118174310
- Full Text :
- https://doi.org/10.3109/08916934.2016.1148692