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Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3.
- Source :
-
Blood [Blood] 2005 Nov 15; Vol. 106 (10), pp. 3490-7. Date of Electronic Publication: 2005 Jul 19. - Publication Year :
- 2005
-
Abstract
- 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a secosteroid hormone that renders dendritic cells (DCs) tolerogenic, favoring the induction of regulatory T cells. Induction of DCs with tolerogenic properties by 1,25(OH)(2)D(3) is associated with increased selective expression of immunoglobulin-like transcript 3 (ILT3), suggesting its involvement in the immunoregulatory properties of this hormone. Here we show an in vivo correlate of the increased ILT3 expression on DCs in healing psoriatic lesions following topical treatment with the 1,25(OH)(2)D(3) analog calcipotriol. Analysis of DC subsets reveals a differential regulation of ILT3 expression by 1,25(OH)(2)D(3), with a marked up-regulation in myeloid DCs but no effect on its expression by plasmacytoid DCs. A regulatory role for ILT3 expressed on DCs is indicated by the increased interferon-gamma (IFN-gamma) secretion promoted by anti-ILT3 addition to cultures of DCs and T cells, but this effect is blunted in 1,25(OH)(2)D(3)-treated DCs, suggesting ILT3-independent mechanisms able to regulate T-cell activation. Although ILT3 expression by DCs is required for induction of regulatory T cells, DC pretreatment with 1,25(OH)(2)D(3) leads to induction of CD4(+)Foxp3(+) cells with suppressive activity irrespective of the presence of neutralizing anti-ILT3 monoclonal antibody (mAb), indicating that ILT3 expression is dispensable for the capacity of 1,25(OH)(2)D(3)-treated DCs to induce regulatory T cells.
- Subjects :
- Antibodies immunology
Antibodies pharmacology
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes pathology
Cells, Cultured
Dendritic Cells pathology
Gene Expression Regulation drug effects
Humans
Interferon-gamma immunology
Interferon-gamma metabolism
Lymphocyte Activation drug effects
Lymphocyte Activation immunology
Membrane Glycoproteins
Psoriasis drug therapy
Psoriasis immunology
Psoriasis pathology
Receptors, Cell Surface immunology
Receptors, Immunologic
Vitamin D immunology
Vitamin D pharmacology
CD4-Positive T-Lymphocytes immunology
Dendritic Cells immunology
Forkhead Transcription Factors immunology
Gene Expression Regulation immunology
Receptors, Cell Surface biosynthesis
Vitamin D analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 106
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 16030186
- Full Text :
- https://doi.org/10.1182/blood-2005-05-2044