Presentation is loading. Please wait.

Presentation is loading. Please wait.

MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated.

Published byOlivia Wheeler Modified over 5 years ago

Similar presentations

Presentation on theme: "MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated."— Presentation transcript:

1 MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4  Enikö Sonkoly, MD, PhD, Peter Janson, PhD, Marja-Leena Majuri, Terhi Savinko, Nanna Fyhrquist, Liv Eidsmo, MD, PhD, Ning Xu, PhD, Florian Meisgen, Tianling Wei, MD, Maria Bradley, MD, PhD, Jan Stenvang, PhD, Sakari Kauppinen, PhD, Harri Alenius, PhD, Antti Lauerma, MD, PhD, Bernhard Homey, MD, PhD, Ola Winqvist, MD, PhD, Mona Ståhle, MD, PhD, Andor Pivarcsi, PhD  Journal of Allergy and Clinical Immunology  Volume 126, Issue 3, Pages e20 (September 2010) DOI: /j.jaci Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 miRNA expression differentiates atopic dermatitis from healthy skin. A, Heat map of miRNA TaqMan array data of skin from healthy subjects (H) and lesional skin from patients with atopic dermatitis (AD). B, Scatter plot of differential miRNA expression according to the significance analysis of microarrays algorithm (upregulated in red and downregulated in green). C, Quantitative real-time PCR analysis of miR-155 in healthy (n = 29) and atopic dermatitis lesional (n = 18) skin. ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Expression of miR-155 in atopic dermatitis skin. A, Flow cytometric analysis of single-cell suspensions from atopic dermatitis skin. B, Numbers of sorted cell populations (left), miR-155 expression as determined by means of quantitative PCR in the sorted cell populations (middle), and estimated contribution of cell populations to total miR-155 (miR-155 expression × number of sorted cells, right). Bars show representative data obtained with cells sorted from one of 3 atopic dermatitis biopsy specimens. C, miR-155 (red) and CD4 (green) expression and 4′-6-diamidino-2-phenylindole dihydrochloride (blue) staining in healthy and atopic dermatitis lesional skin as detected by means of in situ hybridization and immunofluorescence, respectively (original magnification ×400). Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Regulation of miR-155 expression in vitro. A, miR-155 expression in naive T cells, TH1 cells, TH2 cells, and regulatory T (Treg) cells. After stimulation with anti-CD3 and anti-CD28 antibodies, miR-155 levels were quantified on day 3 (pre-mature) and day 7 (mature), as well as in cells restimulated on day 7 with anti-CD3 and anti-CD28 for 24 hours (activated). miR-155 expression was determined by means of quantitative PCR. B, TH1 and TH2 polarization verified by means of IL-5 and IFN-γ ELISA. C, miR-155 expression in PBMCs isolated from healthy donors or patients with atopic dermatitis treated with IL-2, SEB, ConA, or anti-CD3. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Regulation of miR-155 expression in vivo. A, Nonlesional skin of patients with atopic dermatitis (n = 9) was subjected to patch testing with SEB for 0, 2, 6, and 24 hours. B, Nonlesional skin of patients with atopic dermatitis with a history of house dust mite allergy (n = 10) was subjected to atopy patch testing for 0, 2, 6, and 48 hours. miR-155 expression was analyzed by means of quantitative real-time PCR. ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 miR-155 targets CTLA-4 for translational suppression. A, Seed match and sequence alignment of CTLA-4 3′-UTR and miR-155. Gray boxes indicate evolutionary conservation of miR-155 target site. The black rectangle indicates positions of nucleotide mismatches introduced to the miR-155 binding site. B, 3′-UTR luciferase reporter assay with wild-type (WT) or mutated CTLA-4 3′-UTR or no 3′-UTR (empty vector) cotransfected with miR-155 precursor or nontargeting miRNA (control). Relative luciferase activity for 5 separate transfections is shown. C, Intracellular CTLA-4 protein levels in stimulated naive CD4+ cells, as measured by means of flow cytometry, after transfection with miR-155 precursor or control precursor. ∗∗P < .01. n.s., Not significant. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 miR-155 regulates proliferation of T cells. T-cell proliferation measured by means of incorporation of tritiated thymidine after transfection of naive TH cells with either miR-155 precursor, control precursor, or without precursor molecule. Proliferation was measured at days 2 to 3 after restimulation with anti-CD28 antibody and recombinant B7-1/Fc chimera protein. Shown are results from experiments performed on naive CD4+ cells isolated from 4 separate donors. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Expression of miR-155 in human organs and cell types in vitro
Expression of miR-155 in human organs and cell types in vitro. The expression of miR-155 was analyzed by using quantitative real-time PCR in 20 healthy organs and tissues (each a pool of 3 donors), in healthy skin (n = 29), and in lesional atopic dermatitis skin (n = 18; A), as well as in the cellular constituents of the human skin (B). Error bars represent SEMs. Data are expressed in relative units compared with U48 RNA. MDDCs, Monocyte-derived dendritic cells. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Abundance of CD3+, CD86+, and CD20+ cells in atopic dermatitis skin lesions. Immunohistochemical detection of CD3+ cells (T cells; A), CD86+ cells (dendritic cells/macrophages; B), and CD20+ cells (B cells; C) in atopic dermatitis lesional skin. D, Number of cells with a positive staining per view field. Bars represent means + SDs of 9 view fields. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Phenotyping in cell suspensions from atopic dermatitis (AD) skin
Phenotyping in cell suspensions from atopic dermatitis (AD) skin. Gating was set on PBMCs, and live CD45+ cells were analyzed in cell suspensions from 4 biopsy specimens from atopic dermatitis lesional skin (A and B). CD20 staining was analyzed in 1 patient with atopic dermatitis by means of FACS. A, Representative dot plots of CD4+CD3+ cells. B, Representative dot plots of CD11c+HLA-DR+ cells. C, CD20–HLA-DR staining in PBMCs and atopic dermatitis lesional skin. Journal of Allergy and Clinical Immunology  , e20DOI: ( /j.jaci ) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated."

Similar presentations

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,
Identification of drug- and drug-metabolite immune responses originating from both naive and memory T cells  Andrew Gibson, MRes, Lee Faulkner, PhD, Sally.

Identification of drug- and drug-metabolite immune responses originating from both naive and memory T cells  Andrew Gibson, MRes, Lee Faulkner, PhD, Sally.
Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut  Claudia.

Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut  Claudia.
Barbara Stanic, PhD, Willem van de Veen, PhD, Oliver F

Barbara Stanic, PhD, Willem van de Veen, PhD, Oliver F
Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion 

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion 
Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong Th17/Th1 T-cell responses  Anja Hänsel,

Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong Th17/Th1 T-cell responses  Anja Hänsel,
Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions  Asako Ichihara, MD, PhD, Zhongzhi Wang, PhD, Masatoshi Jinnin,

Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions  Asako Ichihara, MD, PhD, Zhongzhi Wang, PhD, Masatoshi Jinnin,
MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis  Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis  Ankit Srivastava, MTech, Pernilla Nikamo, PhD,
CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism  Sabine Ring, PhD, Stephen J. Oliver,

CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions through a CD39, adenosine-dependent mechanism  Sabine Ring, PhD, Stephen J. Oliver,
Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu  Amanda J. Reefer, MS, Kathryn.

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu  Amanda J. Reefer, MS, Kathryn.
Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites 

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites 
Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response  Miriam Wittmann, MD, Mareike Alter, Tanja.

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response  Miriam Wittmann, MD, Mareike Alter, Tanja.
MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration  Dongqing Li, X.I. Li, Aoxue Wang, Florian Meisgen, Andor.

MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration  Dongqing Li, X.I. Li, Aoxue Wang, Florian Meisgen, Andor.
IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation  Regina K. Rowe, MD, PhD, David M. Pyle, MD,

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation  Regina K. Rowe, MD, PhD, David M. Pyle, MD,
Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis  Eva Gros, MSc, Susanne Petzold,

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis  Eva Gros, MSc, Susanne Petzold,
Differential cytokine induction by the human skin–associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control.

Differential cytokine induction by the human skin–associated autoallergen thioredoxin in sensitized patients with atopic dermatitis and healthy control.
Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut  Claudia.

Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut  Claudia.
Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue  Louisa Cheung, Rachel M. Fisher, Natalia Kuzmina,

Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue  Louisa Cheung, Rachel M. Fisher, Natalia Kuzmina,
MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,
IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis  Norbert Meyer, MD, Maya Zimmermann, PhD,

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis  Norbert Meyer, MD, Maya Zimmermann, PhD,

Similar presentations

Ads by Google