Gene regulation by 1,25-dihydroxyvitamin D3 in CD4+CD25+ cells is enabled by IL-2.

Abstract

Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) enhances the immunoregulatory ability of CD4+CD25+ T cells residing in the skin-draining lymph nodes (SDLNs) of mice. The mechanisms responsible were investigated by examining the expression of 84 cytokine and cytokine-related genes in a 96-well gene array. CD4+CD25+ cells isolated from the SDLNs of BALB/c mice, 24 and 96  hours after topical treatment with 1,25(OH)(2)D(3), consistently expressed increased IL-2 mRNA levels and also secreted enhanced quantities of IL-2 after ex vivo stimulation with phorbol 12-myristate 13-acetate and ionomycin. CD4+CD25+ cells from the lymph nodes of naive mice constitutively express the vitamin D receptor, allowing direct modulation by 1,25(OH)(2)D(3). However, in vitro treatment with 1,25(OH)(2)D(3) did not modify the expression of 84 tested cytokine and cytokine-related mRNAs. It was only in the presence of IL-2 that 1,25(OH)(2)D(3) increased the expression of genes including IL-2 and TLR4. Further, 1,25(OH)(2)D(3) enhanced the ability of IL-2 to stimulate CD4+CD25+ cells to proliferate in vitro and also regulate contact hypersensitivity responses on adoptive transfer into naive mice. Therefore, 1,25(OH)(2)D(3) enabled by IL-2 can directly enhance the regulatory potential of CD4+CD25+ T cells to control immune disease.

• Authors: Shelley Gorman, Melinda A Judge, Prue H Hart
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 130 Issue 10 Pg. 2368-76 (Oct 2010) ISSN: 1523-1747 [Electronic] United States
• PMID: 20574434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• Cytokines
• Interleukin-2
• Interleukin-2 Receptor alpha Subunit
• RNA, Messenger
• Receptors, Calcitriol
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Calcitriol

Topics

• Adoptive Transfer
• Animals
• Autoimmune Diseases (drug therapy, genetics, immunology)
• CD4 Antigens (metabolism)
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• Calcitriol (pharmacology)
• Cell Division (drug effects)
• Cell Movement (drug effects)
• Cytokines (genetics)
• Dermatitis, Allergic Contact (drug therapy, genetics, immunology)
• Female
• Gene Expression Regulation (drug effects, immunology)
• In Vitro Techniques
• Interleukin-2 (genetics, metabolism)
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Lymph Nodes (cytology, immunology)
• Mice
• Mice, Inbred BALB C
• Oligonucleotide Array Sequence Analysis
• RNA, Messenger (metabolism)
• Receptors, Calcitriol (genetics)
• Toll-Like Receptor 4 (genetics)