Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma Steven G. Smith, PhD, Akash.

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Presentation transcript:

Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma Steven G. Smith, PhD, Akash Gugilla, BSc, Manali Mukherjee, PhD, Kayla Merim, BSc, Anam Irshad, BSc, Wei Tang, MD, Takashi Kinoshita, MD, Brittany Watson, BSc, John-Paul Oliveria, BSc, Mike Comeau, PhD, Paul M. O'Byrne, MD, Gail M. Gauvreau, PhD, Roma Sehmi, PhD Journal of Allergy and Clinical Immunology Volume 135, Issue 6, Pages 1594-1602 (June 2015) DOI: 10.1016/j.jaci.2014.12.1918 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Fluctuations in sputum and blood HPC (A and B, respectively) and EoP cell (C and D, respectively) counts in patients with mild asthma after diluent (open bars) or allergen (Ag; solid bars) inhalation challenge. HPC and EoP cell counts significantly increased 24 hours after allergen compared with baseline values. Data are mean ± SEM (n = 15). *P < .05 compared with baseline. #P < .05 compared with diluent. Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Changes in sputum HPC expression of TSLPR (A), CD127 (B), and ST2 (C) for diluent (open bars) and allergen (Ag; solid bars) inhalation challenge. Numbers of HPCs expressing TSLPR, ST2, and CD127 significantly increased after allergen. Data are mean ± SEM (n = 10). *P < .05 compared with baseline. #P < .05, Δ comparison with diluent. Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 TSLP and IL-33 priming of HPC (A and B) and EoP cell (C and D) migration. Preincubation with TSLP or IL-33 primed migration of HPCs. TSLP and IL-33 receptor antibody blocked priming (E and F). Data are mean ± SEM (n = 8). *P < .05 compared with diluent. #P < .05 compared with CXCL12. $P < .05 compared with priming response. Ab, Antibody; Dil, diluent; SDF-1α, stromal cell–derived factor 1α. Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Effect of TSLP and IL-33 on intracellular expression of IL-5, IL-13, and IL-4 in HPCs. Incubation for 6 hours with TSLP (1 pg/mL) or IL-33 (1 pg/mL) increased the percentage of HPCs expressing IL-5 (A) or IL-13 (B) but not IL-4 (C). Data are means ± SEMs (n = 12). *P < .05, comparison between response to diluent and various doses of cytokine. Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Effect of receptor blocking antibodies on TSLP- and IL-33–primed migration of HPCs. IL-13Rα blocked priming in both cases (A and C), whereas blocking IL-4Rα had no effect (B and D). Data are means ± SEMs (n = 7). *P < .05 compared with diluent. #P < .05 compared with CXCL12. $P < .05 compared with the priming response. Ab, Antibody; Dil, diluent; SDF-1α, stromal cell–derived factor 1α. Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Priming of HPCs is dependent on incorporation of CXCR4 into GM1-enriched lipid rafts. TSLP (A) and IL-33 (B) priming is inhibited after lipid raft disruption (n = 4). *P < .05 compared with diluent. #P < .05 compared with CXCL12. $P < .05 compared with priming response. Ab, Antibody; Ampho B, amphotericin B; Dil, diluent; Nys, nystatin; SDF-1α, stromal cell–derived factor 1α. Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Journal of Allergy and Clinical Immunology 2015 135, 1594-1602DOI: (10.1016/j.jaci.2014.12.1918) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions