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Kei-ichi Yamanaka, MD, PhD, Charles J. Dimitroff, PhD, Robert C

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Presentation on theme: "Kei-ichi Yamanaka, MD, PhD, Charles J. Dimitroff, PhD, Robert C"— Presentation transcript:

1 Vitamins A and D are potent inhibitors of cutaneous lymphocyte-associated antigen expression 
Kei-ichi Yamanaka, MD, PhD, Charles J. Dimitroff, PhD, Robert C. Fuhlbrigge, MD, PhD, Masato Kakeda, MD, Ichiro Kurokawa, MD, PhD, Hitoshi Mizutani, MD, PhD, Thomas S. Kupper, MD  Journal of Allergy and Clinical Immunology  Volume 121, Issue 1, Pages e3 (January 2008) DOI: /j.jaci Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Normal T cells were cultured with vitamin D or vitamin A. A, CLA expression levels were reduced with 1 nM 1,25D(3), whereas cholecalciferol, an inactive precursor of vitamin D, had no effect. B, CLA expression levels were also decreased with 100 pM RA, 1 nM retinal, and 1 μM retinol (n = 6 per group). ∗Statistical difference: P < .05. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Effect of 1,25D(3) and RA on other lymphocyte trafficking receptors. By using flow cytometry, CLA expression (percent positive and mean fluorescence intensity) was decreased with both vitamins at 1 nM, whereas RA also increased the expression of gut-homing receptors, α4 and β7 integrins, and CCR9 and decreased expression of the LN-homing receptor L-selectin (CD62L). Data are representative of at least 5 independent experiments. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Detection of E- and P-selectin ligands. A, Most CLA+ T cells bound E-selectin/immunoglobulin, and this activity was reduced by treatment with either vitamin A or vitamin D. B, The number of T cells staining positive with P-selectin/immunoglobulin was significantly less after culturing cells in RA, although it was only slightly decreased by treatment with 1,25D(3). Values shown are the percentage of positive cells in each quadrant. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 mRNA levels of glycosyltransferases involved in CLA biosynthesis (A-G) were analyzed on CD3+ T cells cultured with non–growth-inhibitory concentrations of 1,25D(3), RA, or diluent control. At 100 nM, mRNA expression of FucT-VII was significantly decreased by 1,25D(3) and RA treatment. ST3Gal-III mRNA was also significantly decreased by RA (n = 8 per group). ∗Statistical difference: P < .05. C2GnT, Core 2 β1,6 N-acetylglucosaminyltransferase; 6-SulT, N-acetylglucosamine-6-O-sulfotransferase 2. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 A, Western blotting showed that although PSGL-1 expression was unchanged, HECA-452 antigen and E-selectin glycoprotein ligands were eliminated in cells grown with 1,25D(3) or RA. B, Western blotting of anti-PSGL-1 immunoprecipitates showed that although PSGL-1 was expressed, HECA-452 antigen on PSGL-1 from cells treated with 1,25D(3) or RA was eliminated. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 In vivo efficacy of 1,25D(3) and RA in contact hypersensitivity. A, CD4+ T cells were visualized in sections from subcutaneously injected mice (control-treated [i], 1,25D[3]-treated [ii], and RA-treated [iii] mice) and intraperitoneally injected mice (control-treated [iv], 1,25D[3]-treated [v], and RA-treated [vi] mice). CD4+ T cells were routinely detected in control-treated mice (i and iv). Fewer CD4+ cells were detected in 1,25D(3)-treated mice (ii and v) and RA-treated mice (iii and vi) than in control-treated mice. B, The number of skin-infiltrating CD4+ T cells was significantly less in 1,25D(3)- and RA-treated mice. ∗Statistical significance: P < .01. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 CLA expression levels were decreased slightly on 1,25D(3)- or RA-treated cells compared with those seen in control-treated cells on day 3 and significantly after day 5. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Phenotypic analysis on skin-infiltrating CD4+ T cells
Phenotypic analysis on skin-infiltrating CD4+ T cells. Mouse functional E-selectin ligand–positive CD4+ T cells, CCR4+CD4+ T cells, and CCR10+CD4+ T cells were detected in control-treated mice (A); however, the number of these cells was decreased in both groups of vitamin-treated mice (B). Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Foxp3 or IL-7 receptor (IL-7R) expression on skin-infiltrating CD4+ T cells. Foxp3+CD4+ T cells were detected in control-treated mice (A); however, the number of these T cells was reduced by injection of both vitamins (B). Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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