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1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Mar 01; Vol. 180 (5), pp. 2786-95. - Publication Year :
- 2008
-
Abstract
- In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19+ B cells into IgD-CD38+ plasma cells in vitro. A minor proportion of the resulting CD19+IgD-CD38+ cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite of vitamine D3, dramatically increased the proportion of CD19+IgD-CD38+ cells expressing high levels of CCR10. The 1,25-(OH)2D3 also increased the number of CCR10+ cells expressing surface IgA, although the majority of CCR10+ cells remained negative for surface IgA. Thus, 1,25-(OH)2D3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)2D3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)2D3. We confirmed the specific binding of Ets-1 and 1,25-(OH)2D3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)2D3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)2D3.
- Subjects :
- B-Lymphocyte Subsets cytology
Calcitriol metabolism
Cell Line
Cell Line, Transformed
Cell Line, Tumor
Chemotaxis, Leukocyte immunology
Gene Expression Regulation immunology
Humans
Immunity, Mucosal genetics
Promoter Regions, Genetic immunology
Protein Binding immunology
Proto-Oncogene Protein c-ets-1 metabolism
Proto-Oncogene Protein c-ets-1 physiology
Receptors, CCR10 genetics
Receptors, CCR10 metabolism
Receptors, Calcitriol biosynthesis
Receptors, Calcitriol genetics
Receptors, Calcitriol metabolism
Receptors, Calcitriol physiology
Regulatory Sequences, Nucleic Acid immunology
B-Lymphocyte Subsets immunology
B-Lymphocyte Subsets metabolism
Calcitriol physiology
Cell Differentiation immunology
Receptors, CCR10 biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 180
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18292499
- Full Text :
- https://doi.org/10.4049/jimmunol.180.5.2786