Presentation is loading. Please wait.

Presentation is loading. Please wait.

Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology  Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A.

Published byDerek Griffin Modified over 6 years ago

Similar presentations

Presentation on theme: "Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology  Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A."— Presentation transcript:

1 Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology 
Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A. Campbell, PhD, Clare M. Lloyd, PhD  Journal of Allergy and Clinical Immunology  Volume 129, Issue 4, Pages e3 (April 2012) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Identification of in vivo generated TH9 cells. A, Number of TH9 cells in PBMCs from nonallergic and allergic donors. B, Correlation between the number of circulating TH9 cells and plasma IgE levels in humans. C, Percentage of freshly isolated human TH9 cells expressing PU.1. D, TH9 and TH2 cells in the lungs of mice challenged with PBS or HDM for up to 3 weeks. E, Phenotype of murine in vivo generated TH9 cells after 1 week of HDM challenge. F, Allergen specificity of in vivo generated pulmonary T cells. G, Percentage of TH9 cells expressing PU.1 following 1-week HDM challenge in mice. Data shown represent means ± SEMs. ∗P < .05. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Induction of TH9 differentiation in vitro by activin A. A, TH9 cells generated in the presence of IL-4 alone or in association with TGF-β1, activin A, and/or IL-25. B, Percentage of TH9 cells plotted in a histogram. C, Phenotype of TH9 cells differentiated in the presence of IL-4 with either TGF-β1 or activin A. D, IL-9 secretion from activin A–derived TH9 cells after 4 days in culture in the presence of 0.1 ng/mL of TGF-β1. Data shown represent means ± SEMs. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 TH9 Adoptive transfer induces mast cell recruitment to the lungs. A, Schematic of experimental protocol. B, Total cells recovered from the lung 1 week after TH9 cell transfer and challenge with either PBS or HDM. Eosinophils (Siglec F+) (C) and TH2 cells (D) recovered from the lung. Serum mMCP-1 levels (E) and intraepithelial mast cell numbers (F) scored in lung sections expressed as total number of mouse tryptase beta 1 positive cells per lung section. G, Serum IgE levels. IL-13 (H) and IL-9 (I) levels in supernatants from HDM-stimulated LN cell cultures. J, Total cells recovered from the lungs of SCID mice adoptively transferred with TH9 cells and treated with either PBS or HDM. Serum mMCP-1 levels (K) and intraepithelial mast cells numbers (L) in SCID mice. Data shown represent means ± SEMs. ∗P < .05. LN, Lymph node; mMCP-1, mouse mast cell protease-1; NS, not significant; SCID, severe combined immunodeficiency. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Acute blockade of TGF-β and activin A inhibits TH9 differentiation. A, Schematic of experimental protocol. B, TH9 cells recovered from the lung after treatment with either anti–TGF-β and/or anti–activin A in mice challenged with either PBS or HDM. Total cells (C), lung eosinophils (D), and TH2 cells (E) recovered from the lung. Serum mMCP-1 levels (F) and intraepithelial mast cells (G) per lung section. IL-9 (H) and IL-13 (I) levels in supernatants from lymph node cell cultures. J, IL-25 levels in the lungs. Data shown represent means ± SEMs. ∗P < .05. mMCP-1, Mouse mast cell protease-1. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Chronic blockade of TGF-β and activin A reduces airway remodeling. A, Schematic of experimental protocol. B, Peribronchial and perivascular cellular infiltrate (H&E), purple-colored mucin-containing cells in the epithelium (PAS), and perivascular and peribronchiolar collagen (sirrius red) and brown stained intraepithelial mast cells. Original magnification ×40. Scale bar = 50 μm. C, Quantification of mucus positive cells. D, Intraepithelial mast cells per lung section. E, Serum mMCP-1 levels. F, Total lung collagen. G, Total cells recovered from BAL and lung. H, IL-25 levels in the lung. I, Airway resistance (RI) following 3-week HDM challenge. Data shown represent means ± SEMs. ∗P < .05. BAL, Bronchoalveolar lavage; MCPT7, mouse tryptase beta 1; mMCP-1, mouse mast cell protease-1; PAS, periodic acid-Schiff. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 Identification of in vivo generated TH9 cells. A, Representative flow cytometry plot showing IL-9 production by CD4+ cells in the lung after 1 week of HDM challenge or PBS treatment. TH9 cells were defined as CD4+ lymphocytes secreting IL-9 (but not IFN-γ, IL-17, or IL-13). B, Representative flow cytometry plot showing IL-9 isotype control staining. C, Representative flow cytometry plots of NK cells, regulatory T cells, and TH17 cells isolated from the lung following 1 week of intranasal challenge with HDM. These cells do not coexpress IL-9 in response to allergen challenge after 1 week. n = 6. Data are representative of 2 independent experiments. NK, Natural killer. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 HDM challenge increases TGF-β1, IL-25, and activin A levels. A, Histogram overlay of TH9 cells. B, Levels of TGF-β1, activin A, and IL-25 in lung homogenates after 1 week of either PBS or HDM challenge were measured by ELISA. Data represents means ± SEMs from 3 independent experiments (n = 5-8). ∗P < .05. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E3 Adoptive transfer of TH9 cells into BALB/c or SCID mice. A, Representative flow cytometry plot of CD4+IL-13−IL-10−IL-9+ cells before injection into BALB/c mice. B, Representative lung section showing TH9 cells labeled with the cell tracker DIL, around the airways. C, Total cells recovered from the lung from BALB/c mice 1 week after transfer of 106 TH2 control cells and challenge with either PBS or HDM. Eosinophils (Siglec F+) recovered from the lung as determined by flow cytometry. IL-13 and IL-9 levels were measured by ELISA from LN cell cultures stimulated with HDM for 4 days. Serum mMCP-1 levels and intraepithelial mast cell numbers scored in lung sections immunostained with the murine mast cell marker MCPT7 and expressed as total number of MCPT7 positive cells per lung section. Data shown represent means ± SEMs of 2 independent experiments (n = 4-8). D, Representative flow cytometry plot of CD3+CD4+ cells recovered from the lungs and LNs of SCID mice adoptively transferred with either TH2 or TH9 cells and treated with HDM. ∗P < .05. LN, Lymph node; mMCP-1, mouse mast cell protease-1; SCID, severe combined immunodeficiency. Journal of Allergy and Clinical Immunology  , e3DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology  Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A."

Similar presentations

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease  Ana Paula Moreira, PhD, Karen A.

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease  Ana Paula Moreira, PhD, Karen A.
Water-soluble chitosan inhibits nerve growth factor and attenuates allergic inflammation in mite allergen–induced allergic rhinitis  Pei-Chi Chen, MSc,

Water-soluble chitosan inhibits nerve growth factor and attenuates allergic inflammation in mite allergen–induced allergic rhinitis  Pei-Chi Chen, MSc,
Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity  Laetitia Everaere, PhD, Saliha Ait-Yahia, PhD, Olivier Molendi-Coste,

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity  Laetitia Everaere, PhD, Saliha Ait-Yahia, PhD, Olivier Molendi-Coste,
Exposure to allergen and diesel exhaust particles potentiates secondary allergen- specific memory responses, promoting asthma susceptibility  Eric B. Brandt,

Exposure to allergen and diesel exhaust particles potentiates secondary allergen- specific memory responses, promoting asthma susceptibility  Eric B. Brandt,
Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A

Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A
Therapeutic reversal of food allergen sensitivity by mature retinoic acid–differentiated dendritic cell induction of LAG3+CD49b−Foxp3− regulatory T cells 

Therapeutic reversal of food allergen sensitivity by mature retinoic acid–differentiated dendritic cell induction of LAG3+CD49b−Foxp3− regulatory T cells 
Thymic stromal lymphopoietin signaling in CD4+ T cells is required for TH2 memory  Qun Wang, PhD, Jianguang Du, PhD, Jingjing Zhu, MSc, Xiaowei Yang, MSc,

Thymic stromal lymphopoietin signaling in CD4+ T cells is required for TH2 memory  Qun Wang, PhD, Jianguang Du, PhD, Jingjing Zhu, MSc, Xiaowei Yang, MSc,
Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme  Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,

Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme  Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,
CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation  Jae-Won Oh, MD, PhD, Christine M. Seroogy,

CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation  Jae-Won Oh, MD, PhD, Christine M. Seroogy,
The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF- like (BATF), regulates lymphocyte- and mast cell–driven immune.

The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF- like (BATF), regulates lymphocyte- and mast cell–driven immune.
Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model  Sylvie Amu, PhD, Sean P.

Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model  Sylvie Amu, PhD, Sean P.
The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF- like (BATF), regulates lymphocyte- and mast cell–driven immune.

The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF- like (BATF), regulates lymphocyte- and mast cell–driven immune.
Robert J. Snelgrove, PhD, Lisa G

Robert J. Snelgrove, PhD, Lisa G
IL-25 and CD4+ TH2 cells enhance type 2 innate lymphoid cell–derived IL-13 production, which promotes IgE-mediated experimental food allergy  Jee-Boong.

IL-25 and CD4+ TH2 cells enhance type 2 innate lymphoid cell–derived IL-13 production, which promotes IgE-mediated experimental food allergy  Jee-Boong.
Allergy prevention starts before conception: Maternofetal transfer of tolerance protects against the development of asthma  Tobias Polte, PhD, Christian.

Allergy prevention starts before conception: Maternofetal transfer of tolerance protects against the development of asthma  Tobias Polte, PhD, Christian.
Interferon response factor 3 is essential for house dust mite–induced airway allergy  Thomas Marichal, DVM, Denis Bedoret, DVM, PhD, Claire Mesnil, DVM,

Interferon response factor 3 is essential for house dust mite–induced airway allergy  Thomas Marichal, DVM, Denis Bedoret, DVM, PhD, Claire Mesnil, DVM,
Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation 

Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation 
Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity  Jillian L. Barlow, PhD, Agustin Bellosi,

Innate IL-13–producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity  Jillian L. Barlow, PhD, Agustin Bellosi,
Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma  Frank Kirstein, PhD, William G.C.

Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma  Frank Kirstein, PhD, William G.C.
Frank Kirstein, PhD, Natalie E

Frank Kirstein, PhD, Natalie E

Similar presentations

Ads by Google