Presentation is loading. Please wait.

Presentation is loading. Please wait.

Ton C. Doan, BA, Brian M. Jeong, MSc, Mackenzie E. Coden, BA, Lucas F

Published byVerawati Hermanto Modified over 5 years ago

Similar presentations

Presentation on theme: "Ton C. Doan, BA, Brian M. Jeong, MSc, Mackenzie E. Coden, BA, Lucas F"— Presentation transcript:

1 Matrix protein tenascin-C expands and reversibly blocks maturation of murine eosinophil progenitors 
Ton C. Doan, BA, Brian M. Jeong, MSc, Mackenzie E. Coden, BA, Lucas F. Loffredo, BSc, Swati Bhattacharyya, PhD, Sergio E. Chiarella, MD, John Varga, MD, Hiam Abdala-Valencia, PhD, Sergejs Berdnikovs, PhD  Journal of Allergy and Clinical Immunology  Volume 142, Issue 2, Pages e4 (August 2018) DOI: /j.jaci Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 A, Protocol for bone marrow and ex vivo lung eosinophil differentiation culture, separated into 3 critical phases: precursor expansion, eosinophil commitment, and eosinophil maturation. Cells were cultured with SCF and FLT3L for 4 days before induction to eosinophil commitment via IL-5. B, Expression of Siglec-F (eosinophil marker) and Sca-1 (stem cell marker) on CD45+ cells at terminal bone marrow culture end point on day 15. Control culture consistently resulted in more than 90% Siglec-F+Sca-1− eosin-positive eosinophils. Morphology of these cells is shown in cytospin preparations stained with differential staining solution. C, Kinetics of bone marrow–derived eosinophil differentiation and Sca-1 expression on CD45+Siglec-F+/− by flow cytometry. Asterisks denote differences between each time point and day 3 culture start time point for each of the treatment curves; asterisk color matches treatment curve color. D, Quantification of CD45+Sca-1+ cells by flow cytometry in bone marrow–derived eosinophil cultures. Blue, control culture; green, TNC-supplemented culture; asterisks denote differences between 2 cultures. E, Kinetics of expression of IL-5Rα on cells throughout bone marrow culture quantified by flow cytometry. TNC significantly downregulated IL-5 receptor during days 5 and 7 of culture (IL-5–induced eosinophil lineage commitment phase); 3 wells/treatment/culture time point, N = 3 independent donor cultures. SCF, Stem cell factor; SSC, side scatter. *P < .05. ****P < .0001. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 A, Withdrawal of TNC from day 6 bone marrow culture rescued IL-5–induced eosinophil commitment. MFI levels of Sca-1 on CD45+Siglec-F+ eosinophils on day 15 of the culture are shown. Cytospin preparations confirmed restoration of mature eosinophil phenotype after TNC withdrawal. B, Quantification of CD45+Siglec-F+ eosinophils on day 15 of bone marrow culture. Withdrawal of TNC on day 6 doubled the yield of mature eosinophils. C, In a model of allergic inflammation, TNC−/− mice had a significant reduction in both common myeloid progenitors (CD45+c-kit+CD34+ population, top scatterplots) and Lin− CD45+Siglec-F+Sca-1+ eosinophil progenitors (Lineage expression shown out of CD45+Siglec-F+Sca-1+ parent population, bottom histograms). N = 8 for WT, N = 4 for TNC−/− mice. The experiment was repeated twice. D, IL-5 culture of ex vivo lung homogenates. Lineage histograms shown are out of CD45+Siglec-F+Sca-1+ parent gates. Eosinophils from TNC−/− lungs showed accelerated maturation and reduced numbers of Lin−Siglec-F+Sca-1+ cells, whereas TNC peptide addition reversed this effect. Bar graphs on the left show normalized mature eosinophil counts (out of total structural and hematopoietic cells) in cytospin preparations of the whole lung ex vivo cultures (40×, 10 different fields scored/treatment). Bar graphs on the right quantify the percentage of Sca-1+Lin− cells out of the total population of Siglec-F+ cells in IL-5 culture of ex vivo lung homogenates; 3 wells/treatment/culture time point, N = 2-3 independent donor cultures. MFI, Median fluorescence intensity. *P < .05. **P < .01. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig E1 Total cell counts in bone marrow–derived eosinophil cultures. Blue, control culture; green, TNC-supplemented culture; 3 wells/treatment/culture time point, N = 3 independent donor cultures. Asterisks denote differences between 2 cultures for each corresponding time point. *P < .05. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E2 Expression of IL-5Rα on CD45+Siglec-F+ eosinophil progenitors at day 6 in bone marrow culture. FMO, Fluorescence Minus One. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E3 Quantification of flow cytometry data shown in Fig 2, C. *P < .05. ****P < .0001. Journal of Allergy and Clinical Immunology  , e4DOI: ( /j.jaci ) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Ton C. Doan, BA, Brian M. Jeong, MSc, Mackenzie E. Coden, BA, Lucas F"

Similar presentations

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,
Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses  Katrien C. De Grove, MSc, Sharen Provoost,

Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses  Katrien C. De Grove, MSc, Sharen Provoost,
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,
Surface availability of beta-glucans is critical determinant of host immune response to Cladosporium cladosporioides  Rachael A. Mintz-Cole, PhD, Eric.

Surface availability of beta-glucans is critical determinant of host immune response to Cladosporium cladosporioides  Rachael A. Mintz-Cole, PhD, Eric.
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.
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,
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.
Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4–dependent dermal dendritic cells  Julie Deckers, MSc, Dorine.

Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4–dependent dermal dendritic cells  Julie Deckers, MSc, Dorine.
IL-4 induces IL-13–independent allergic airway inflammation

IL-4 induces IL-13–independent allergic airway inflammation
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.
IL-4 blocks TH1-polarizing/inflammatory cytokine gene expression during monocyte- derived dendritic cell differentiation through histone hypoacetylation 

IL-4 blocks TH1-polarizing/inflammatory cytokine gene expression during monocyte- derived dendritic cell differentiation through histone hypoacetylation 
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,
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.
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,
Frank Kirstein, PhD, Natalie E

Frank Kirstein, PhD, Natalie E
Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring  Phoebe K. Richgels, MS, Amnah.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring  Phoebe K. Richgels, MS, Amnah.
Nazanin Farhadi, MSc, Laura Lambert, BA, Chiara Triulzi, PhD, Peter J

Nazanin Farhadi, MSc, Laura Lambert, BA, Chiara Triulzi, PhD, Peter J
Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival  Jyoti Balhara, MSc, Lianyu Shan,

Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival  Jyoti Balhara, MSc, Lianyu Shan,
Type 2 innate lymphoid cells in induced sputum from children with severe asthma  Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.

Type 2 innate lymphoid cells in induced sputum from children with severe asthma  Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.
IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin  Robert J. Salmond, PhD, Ananda S. Mirchandani,

IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin  Robert J. Salmond, PhD, Ananda S. Mirchandani,

Similar presentations

Ads by Google