Presentation is loading. Please wait.

Presentation is loading. Please wait.

Tacrolimus and TGF-β act synergistically on the generation of Langerhans cells  Bartlomiej Kwiek, MD, Wen-Ming Peng, MSc, Jean-Pierre Allam, MD, Andrzej.

Published byRalf Todd Modified over 5 years ago

Similar presentations

Presentation on theme: "Tacrolimus and TGF-β act synergistically on the generation of Langerhans cells  Bartlomiej Kwiek, MD, Wen-Ming Peng, MSc, Jean-Pierre Allam, MD, Andrzej."— Presentation transcript:

1 Tacrolimus and TGF-β act synergistically on the generation of Langerhans cells 
Bartlomiej Kwiek, MD, Wen-Ming Peng, MSc, Jean-Pierre Allam, MD, Andrzej Langner, MD, Thomas Bieber, MD, PhD, Natalija Novak, MD  Journal of Allergy and Clinical Immunology  Volume 122, Issue 1, Pages e1 (July 2008) DOI: /j.jaci Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Tacrolimus enhances the effect of TGF-β1 on LC-like DC generation in vitro. The gating strategy is shown in panel A. In the absence of exogenous TGF-β1, the expression of Langerin (B) and E-cadherin (C) is low. Along with the increased concentration of TGF-β1 (1 ng/mL TGF-β1; 10 ng/mL TGF-β1), the expression of E-cadherin and Langerin is augmented. Representative dot plots with the percentage of positive CD1a+ DCs depicted in the right corner are shown. CD1a+ DCs cultured with low-dose TGF-β1 and tacrolimus expressed more Langerin (D) and E-cadherin (E) than LCs-DCs treated with a low dose of TGF-β1 alone and resemble LCs treated with a high dose of TGF-β1 (n = 7). SSC-H, Sideward scatter; FSC-H, forward scatter; 7AAD, 7-amino-actinomycin-D; Tac, tacrolimus. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Tacrolimus amplifies the effect of TGF-β1 on the expression of costimulatory molecules of LC-like DCs. Tacrolimus synergized the effect of TGF-β1, upregulating the expression of CD40 (F) and downregulating the expression of costimulatory molecules and MHC II (B-E), but did not display any additional effect on MHC I expression (A). ∗P < .05, ∗∗P < .01 (n = 10). Tac, Tacrolimus. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 A-E, Tacrolimus synergizes the inhibitory effect of TGF-β1 on DC maturation. Tacrolimus aggravates the TGF-β1–mediated downregulation of CD80, CD83, CD86, and MHC II on mature DCs. ∗P < .05, ∗∗P < .01 (n = 6). Tac, Tacrolimus. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Tacrolimus enhances the suppressive effect of TGF-β1 on the stimulatory capacity of DCs toward T cells. Addition of tacrolimus to 1 ng/mL TGF-β1 (low TGF-β) resulted in the reduction of the stimulatory capacity of DCs at an antigen-presenting cell/T-cell ratio of 1:100 in comparison with the condition with low TGF-β1 alone in both immature DCs (A) and mature DCs with the addition of TNF-α (250 U/mL; B). Averages of triplicates of 10 experiments are presented as means ± SEMs, and the relative stimulation index is depicted on the y-axis and calculated as follows: rSI=cpm(mixedlymphocytereaction)−cpm(Tcell)/cpm(Tcell). ∗P < .05, ∗∗P < .01, and ∗∗∗P < Tac, Tacrolimus. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Treatment of AD with tacrolimus 0.1% ointment results in increased numbers of CD1a+/Langerin-positive/Lag+ cells in the epidermis. A-F, Images of microscopic evaluation of skin biopsy specimens for the expression of CD1a, as well as the LC markers Langerin and Lag, for 1 of 5 representative patients are presented. G, Results of a total of 5 experiments are shown. The number of CD1a+ epidermal cells before tacrolimus treatment significantly exceeds the number of Langerin-positive and Lag+ cells, indicating the existence of a CD1a+ non-LC population of DCs in the epidermis of patients with AD. After 1 week of tacrolimus application, the total number of epidermal CD1a+ DCs increased simultaneously with the increased amount of Langerin-positive and Lag+ LCs. Values are presented as means ± SEMs. ∗P < .05 and ∗∗P < .01 (n = 5). Bar = 100 μm. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Higher TGF-β receptor II expression of DCs cultured with TGF-β and tacrolimus on day 2 of culture and TGF-β2 production of HaCat cells. A, Mean ± SEM of the RFI of the extracellular expression of TGF-β receptor II of differentiating DCs on day 2 of culture is shown (n = 8 experiments). B, Amount of TGF-β1 in the supernatant of HaCat cells stimulated with increasing amounts of tacrolimus, 10−9 to 10−7 mol/L, with or without TNF-α is shown as the mean ± SEM value of 3 experiments. Tac, Tacrolimus. ∗P < .05. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Tacrolimus and TGF-β act synergistically on the generation of Langerhans cells  Bartlomiej Kwiek, MD, Wen-Ming Peng, MSc, Jean-Pierre Allam, MD, Andrzej."

Similar presentations

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells  Claire S. Leitch, MBChB (Hons), MMed Sci, Eenass Natafji,

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells  Claire S. Leitch, MBChB (Hons), MMed Sci, Eenass Natafji,
TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis  Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.

TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis  Maya Zimmermann, PhD, Andrea Koreck, MD, Norbert.
Multiple-checkpoint inhibition of thymic stromal lymphopoietin–induced TH2 response by TH17-related cytokines  Sofia I. Bogiatzi, BSc, Maude Guillot-Delost,

Multiple-checkpoint inhibition of thymic stromal lymphopoietin–induced TH2 response by TH17-related cytokines  Sofia I. Bogiatzi, BSc, Maude Guillot-Delost,
Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function  Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function  Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,
Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2  Natalija Novak, MD, Nihal Mete, MD, Caroline.

Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2  Natalija Novak, MD, Nihal Mete, MD, Caroline.
Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma  Chun-Yu Lo, MD, Charalambos Michaeloudes,

Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma  Chun-Yu Lo, MD, Charalambos Michaeloudes,
Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy  Yin Yao, MD, Cai-Ling.

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy  Yin Yao, MD, Cai-Ling.
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 
Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema  Laura Maintz, MD, Said Benfadal, Jean-Pierre Allam,

Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema  Laura Maintz, MD, Said Benfadal, Jean-Pierre Allam,
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,
Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells  Claire S. Leitch, MBChB (Hons), MMed Sci, Eenass Natafji,

Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells  Claire S. Leitch, MBChB (Hons), MMed Sci, Eenass Natafji,
Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4 inhibitor treatment  Lennart M. Roesner, PhD, Petra Kienlin, Gabriele.

Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4 inhibitor treatment  Lennart M. Roesner, PhD, Petra Kienlin, Gabriele.
Targeting Toll-like receptors on dendritic cells modifies the TH2 response to peanut allergens in vitro  Pierre Pochard, PhD, Brian Vickery, MD, M. Cecilia.

Targeting Toll-like receptors on dendritic cells modifies the TH2 response to peanut allergens in vitro  Pierre Pochard, PhD, Brian Vickery, MD, M. Cecilia.
Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization  Silvia.

Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization  Silvia.
Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells  Shuo Li, PhD, Hideaki Morita, MD, PhD, Beate Rückert, Sci Tec, Tadech.

Type 3 innate lymphoid cells induce proliferation of CD94+ natural killer cells  Shuo Li, PhD, Hideaki Morita, MD, PhD, Beate Rückert, Sci Tec, Tadech.
Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin  Mohan S. Maddur, DVM, Janakiraman Vani,

Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin  Mohan S. Maddur, DVM, Janakiraman Vani,
IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis  James G. Krueger, MD, Scott Fretzin, MD, Mayte Suárez-Fariñas,

IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis  James G. Krueger, MD, Scott Fretzin, MD, Mayte Suárez-Fariñas,
Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells  Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,

Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells  Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,
Signaling through FcRγ-associated receptors on dendritic cells drives IL-33–dependent TH2-type responses  Melissa Y. Tjota, BA, Cara L. Hrusch, PhD, Kelly.

Signaling through FcRγ-associated receptors on dendritic cells drives IL-33–dependent TH2-type responses  Melissa Y. Tjota, BA, Cara L. Hrusch, PhD, Kelly.
Glucocorticoids promote intrinsic human TH17 differentiation

Glucocorticoids promote intrinsic human TH17 differentiation

Similar presentations

Ads by Google