Calcitriol modulates the CD46 pathway in T cells.
The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3483209?pdf=render |
| _version_ | 1811295127034920960 |
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| author | Karoline Kickler Siobhan Ni Choileain Anna Williams Anna Richards Anne L Astier |
| author_facet | Karoline Kickler Siobhan Ni Choileain Anna Williams Anna Richards Anne L Astier |
| author_sort | Karoline Kickler |
| collection | DOAJ |
| description | The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)(2)D(3) or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNγ ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS. |
| first_indexed | 2024-04-13T05:27:56Z |
| format | Article |
| id | doaj.art-c4b235911a814495a33c2950e38be486 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T05:27:56Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c4b235911a814495a33c2950e38be4862022-12-22T03:00:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4848610.1371/journal.pone.0048486Calcitriol modulates the CD46 pathway in T cells.Karoline KicklerSiobhan Ni ChoileainAnna WilliamsAnna RichardsAnne L AstierThe complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)(2)D(3) or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNγ ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS.http://europepmc.org/articles/PMC3483209?pdf=render |
| spellingShingle | Karoline Kickler Siobhan Ni Choileain Anna Williams Anna Richards Anne L Astier Calcitriol modulates the CD46 pathway in T cells. PLoS ONE |
| title | Calcitriol modulates the CD46 pathway in T cells. |
| title_full | Calcitriol modulates the CD46 pathway in T cells. |
| title_fullStr | Calcitriol modulates the CD46 pathway in T cells. |
| title_full_unstemmed | Calcitriol modulates the CD46 pathway in T cells. |
| title_short | Calcitriol modulates the CD46 pathway in T cells. |
| title_sort | calcitriol modulates the cd46 pathway in t cells |
| url | http://europepmc.org/articles/PMC3483209?pdf=render |
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