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Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation 

Published byΜύρων Βουγιουκλάκης Modified over 5 years ago

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Presentation on theme: "Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation "— Presentation transcript:

1 Selective control of SIRP-α–positive airway dendritic cell trafficking through CD47 is critical for the development of TH2-mediated allergic inflammation  Marianne Raymond, MSc, Manuel Rubio, BSc, Geneviève Fortin, BSc, Karim Hamdy Shalaby, BSc, Hamida Hammad, PhD, Bart N. Lambrecht, MD, PhD, Marika Sarfati, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 124, Issue 6, Pages e1 (December 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 CD11bhighCD103-DCs preferentially expressed SIRP-α and are recruited during allergic airway inflammation. A, Immunization procedure. B, Lung sections stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). C, BALF cell numbers. CD103 and CD11b expression gated on CD11c+ DCs in lungs (D) and mLNs (E). SIRP-α and CD47 expression gated on CD11c+CD11blowCD103+(red) and CD11c+CD11bhighCD103-(blue) cells. Percentage and absolute numbers of lung (F) and mLN (G) DC subsets, means ± SEMs (5-10 mice/group). IP, Intraperitoneal; OVA, ovalbumin; PE, phycoerythrin. ∗∗∗P < .001; ∗∗P < .01. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 CD47 deficiency reduces the severity of experimental allergic asthma. A, Resistance to various doses of methacholine of CD47+/+ and CD47-/- sensitized and challenged mice. B, Lung sections stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). Data are representative of 5 individually analyzed lungs. C, BALF cell numbers. Means ± SEMs (5-10 mice/group). OVA, Ovalbumin; Eosino, Eosinophiles; Neutro, neutrophiles; Lympho, lymphocytes; Mono, monocytes. ∗∗P < .01; ∗P < .05. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 CD47 selectively controls airway CD11bhighCD103-SIRP-α+ DC migration at steady state and during allergic airway disease. A, CD11chigh/I-A+ (mDCs) and CD11clow/B G8+ (pDCs; left) and mDC/pDC ratio (right). Percentage and absolute numbers of DCs subsets (gated on CD11c+) in mLNs (B) and lung (C) (8-10 mice/group). D, Naive CD47+/+ and CD47-/- mice injected intratracheally with FITC-conjugated microspheres and CD11c+FITC+ cells in mLNs (E) and BALF (F). Means ± SEMs (3 mice/group). OVA, Ovalbumin. ∗∗∗P < .001; ∗∗P < .01; ∗P < .05. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 CD47 regulates airway SIRP-α+ DC–driven TH2 responses. A,left, Percentage of CD4+ T cells in mLN. A,right, Proliferation and (B and C) cytokine release after ovalbumin (OVA) restimulation in vitro. D, CD4+FoxP3+ T cells. Total (E) and OVA-specific (F) immunoglobulin in sera (5-20 mice/group). G and H, After adoptive transfer and immunization, CFSE-labeled transgenic cells were retraced in mLNs (divided [left], MFI and undivided cells [middle]) and iLNs (mean of 5-7 mice/group). CPM, Counts per minute; IP, intraperitoneal; IV, intravenous; iLN, Inguinal lymph nodes. ∗∗∗P < .001; ∗∗P < .01. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Local delivery of SIRP-α+CD47+/+ DCs elicits a strong TH2 response in CD47-/- mice. A, Sensitized mice were instilled intratracheally (IT) with ovalbumin (OVA)–pulsed or PBS-pulsed BMDCs. B, IL-4, IL-5, and IL-13 production were measured in the supernatant of mLN cell cultures. Serum levels of OVA-specific IgE (C) and number of eosinophils in the BALF (D). Means ± SEMs (4-7 mice/group). IP, Intraperitoneal. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 CD47 expression on SIRP-α+ DCs is required to promote TH2-mediated airway inflammation. A, Ovalbumin (OVA)–pulsed BMDCs sensitized mice received 3 OVA-aerosol challenges. B, Lung sections stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). One representative of 5 individually analyzed lungs. C, IL-4, IL-5, and IL-13 levels in the supernatants of mLN cell cultures after in vitro restimulation with OVA. Means ± SEMs (8 mice/group). IT, Intratracheal. ∗∗P < .01; ∗P < .05. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 7 Targeting CD47 protects BALB/c mice from TH2-mediated airway allergic inflammation. A, Immunization and treatment procedure. B, Lung sections stained with hematoxylin (H&E) and periodic acid-Schiff (PAS). C, BALF cell numbers. Ovalbumin (OVA)–specific IgE in sera (D) and TH2 cytokine release in mLN culture (4-8 mice/group) (E). F, CFSE-labeled transgenic cells retraced in mLNs after adoptive transfer and immunization with or without SIRP-α-Fc treatment (mean of 5-6 mice/group). IP, Intraperitoneal. ∗∗P < .01; ∗P < .05. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Phenotype and functional properties of BMDCs
Phenotype and functional properties of BMDCs. A and B, Phenotype of ovalbumin (OVA)–pulsed CD47+/+ or CD47-/- BMDCs. Shown is 1 representative experiment of 3. C, CD47+/+ or CD47-/- BMDCs were cultured with transgenic CD47-/-CD4+ T cells in the presence of OVA peptide under TH2-polarizing conditions (IL-4 and anti–IFN-γ), and IL-4 secretion was measured in the supernatant. Means ± SDs of 3 independent experiments. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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