1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells.
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.
Shirakawa
Aiko-Konno
AK
Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
Nagakubo
Daisuke
D
Hieshima
Kunio
K
Nakayama
Takashi
T
Jin
Zhe
Z
Yoshie
Osamu
O
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism / Q000502:physiology; D054447:Receptors, CCR10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology
C515706:CCR10 protein, human; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D054447:Receptors, CCR10; D018167:Receptors, Calcitriol; D002117:Calcitriol