Presentation is loading. Please wait.

Presentation is loading. Please wait.

Regulated in development and DNA damage responses 1 (REDD1) links stress with IL- 1β–mediated familial Mediterranean fever attack through autophagy-driven.

Published byAbner Gilbert Modified over 6 years ago

Similar presentations

Presentation on theme: "Regulated in development and DNA damage responses 1 (REDD1) links stress with IL- 1β–mediated familial Mediterranean fever attack through autophagy-driven."— Presentation transcript:

1 Regulated in development and DNA damage responses 1 (REDD1) links stress with IL- 1β–mediated familial Mediterranean fever attack through autophagy-driven neutrophil extracellular traps  Panagiotis Skendros, MD, PhD, Akrivi Chrysanthopoulou, PhD, François Rousset, MSc, Konstantinos Kambas, PhD, Athanasios Arampatzioglou, MSc, Alexandros Mitsios, BSc, Veronique Bocly, BSc, Theocharis Konstantinidis, MD, Philippe Pellet, BSc, Iliana Angelidou, MSc, Eirini Apostolidou, MD, Dimitrios Ritis, MSc, Victoria Tsironidou, BSc, Sotiris Galtsidis, PhD, Charalampos Papagoras, MD, PhD, Dimitrios Stakos, MD, PhD, Georgios Kouklakis, MD, PhD, Vasiliki Dalla, MD, PhD, Maria Koffa, PhD, Ioannis Mitroulis, MD, PhD, Ioannis Theodorou, MD, PhD, Konstantinos Ritis, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 140, Issue 5, Pages e13 (November 2017) DOI: /j.jaci Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Journal of Allergy and Clinical Immunology 2017 140, 1378-1387
Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 1 REDD1 overexpression during FMF attacks. A and B, Transcriptomic (Fig 1, A) and heat map (Fig 1, B; false discovery rate < 0.05) analysis between neutrophils from patients with FMF attacks and neutrophils from patients in remission (n = 3). In Fig 1, A, β-tubulin (TUBB) is displayed as a negative control. C and D, REDD1 mRNA levels (Fig 1, C; n = 6) and REDD1 or p62/SQSTM1 immunoblotting (Fig 1, D; n = 4) in neutrophils from patients with FMF attacks in comparison with neutrophils from patients in FMF remission and those from control subjects. In Fig 1, A and C, data are presented as means ± SDs. ∗P < .05. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 2 REDD1 induction leads to autophagy-mediated NET release. A, Induction of REDD1 in neutrophils from patients in FMF remission compared with neutrophils from control subjects. B and C, REDD1-induced autophagy assessed with LC3B staining (red, LC3B; blue, 4′,6-diamidino-2-phenylindole [DAPI]/DNA; Fig 2, B) or p62/SQSTM1 immunoblotting (Fig 2, C). D and E, REDD1-induced NET release is autophagy mediated. F, Induction of NET release in neutrophils from patients in FMF remission compared with those from control subjects. G, REDD1 expression in neutrophils from control subjects compared with those from patients in FMF remission treated with sera from patients with FMF attacks. H, Induction of NET release in neutrophils from patients in FMF remission. Fig 2, D and H, Green, neutrophil elastase (NE); red, CitH3. In Fig 2, A-H, n = 6. Bars show means ± SDs. ∗P < .05. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 3 The microenvironment in patients with FMF attacks is required for IL-1β expression on REDD1-induced NETs. Neutrophils from patients in FMF remission were treated with REDD1 inducer, sera from patients with FMF attacks, and a combination of these, as assessed by means of confocal microscopy (green, IL-1β, red, neutrophil elastase [NE]; A) and immunoblotting of purified NET proteins (B; n = 4). Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 4 Regulation of IL-1β bioactivity by REDD1-induced autolysosomes in neutrophils. A-C, Neutrophils from control subjects (Fig 4, A) or neutrophils from patients in FMF remission (Fig 4, B) treated with sera from patients with FMF attacks in the presence of REDD1 inducer (10 μmol/L) and ex vivo isolated neutrophils from patients with FMF attacks (Fig 4, C; magenta, REDD1; green, pyrin or NALP3; red, LysoTracker). D and E, IL-1β expression in purified NET proteins (Fig 4, D) or on isolated NET structures from neutrophils from control subjects or neutrophils from patients in FMF remission on treatment with sera from patients with FMF attacks in the presence of REDD1 inducer (10 μmol/L; Fig 4, E). F, IL-1β protein expression in PBMCs from control subjects treated with NET structures generated by double-stimulated neutrophils from patients in FMF remission or control subjects. Fig 4, A-F, n = 4. Data are presented as means ± SDs. IOD, Integrated optical density. ∗P < .05. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 5 Effect of epinephrine in neutrophils from patients in FMF remission. A, REDD1 expression levels in neutrophils treated with epinephrine (1 nmol/L; mean ± SD). B, NET release from neutrophils treated with epinephrine (1 nmol/L) in the presence or absence of sera from patients with FMF attacks (green, IL-1β; red, neutrophil elastase [NE]). Fig 5, A and B, n = 4. ∗P < .05. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 6 REDD1 expression in patients with inflammatory diseases. A and B, REDD1 expression in neutrophils from patients with FMF attacks, active AOSD, or acute bacterial infections compared with healthy control subjects (Fig 6, A) and in neutrophils from control subjects treated with corresponding serum (Fig 6, B). Data are presented as means ± SDs. n.s., Not significant. ∗P < .05. C, Heat map analysis of REDD1 expression between neutrophils from selected similarly aged patients (FMF, AOSD, infections) with attack and those from the same patients in remission and after in vitro stimulation of neutrophils from control subjects with corresponding serum. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig 7 Neutrophil IL-1β/CitH3 expression in patients with inflammatory diseases. Representative scatter plots (A) and data from flow cytometry of CitH3-positive and/or IL-1β–positive ex vivo isolated neutrophils from patients with autoinflammatory diseases compared with those from patients with infections or healthy control subjects (B-D). In Fig 7, B and C, data are presented as means ± SDs. n.s., Not significant. ∗P < .05. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E1 Differentially expressed genes between patients with FMF in remission and control subjects (cutoff false discovery rate < 0.05). β-Tubulin (TUBB) is displayed as a negative control and has no difference of expression. Data are presented as means ± SDs. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Fig E2 Increase in the autophagy level of neutrophils from patients in FMF remission in the presence of a high dose of REDD1 inducer. Autophagy induction assessed with LC3B staining in neutrophils from patients in FMF remission treated with different doses of REDD1 inducer are shown (confocal microscopy; red, LC3B; blue, 4′,6-diamidino-2-phenylindole [DAPI]/DNA; n = 6). Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Fig E3 IL-1β protein expression in PBMCs from control subjects treated with NET structures derived from neutrophils from control subjects on treatment with sera from patients with FMF attacks in the presence of REDD1 inducer (10 μmol/L; n = 4). Anakinra was used as an inhibitor of IL-1β signaling. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

13 Fig E4 Expression of IL-1β on NETs released from neutrophils obtained from patients with AOSD. Localization of IL-1β in NETs from patients with AOSD during active disease compared with those released from patients with bacterial infections is shown (confocal microscopy; green, IL-1β; red, neutrophil elastase [NE]; blue, 4′,6-diamidino-2-phenylindole [DAPI]/DNA; n = 5). Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

14 Fig E5 IL-1β/CitH3 expression in neutrophils from control subjects stimulated in vitro with sera from patients with FMF attacks or sepsis or healthy control sera. Representative scatter plots (A) and data from flow cytometry of CitH3- or IL-1β–positive neutrophils (B and C) are shown. In Fig E5, B and C, data are presented as means ± SDs. Fig E5, B and C, n = 5. ∗P < .05. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Regulated in development and DNA damage responses 1 (REDD1) links stress with IL- 1β–mediated familial Mediterranean fever attack through autophagy-driven."

Similar presentations

Maria B. Sukkar, PhD, Shaoping Xie, PhD, Nadia M

Maria B. Sukkar, PhD, Shaoping Xie, PhD, Nadia M
Asthmatic airway epithelial cells differentially regulate fibroblast expression of extracellular matrix components  Stephen R. Reeves, MD, PhD, Tessa.

Asthmatic airway epithelial cells differentially regulate fibroblast expression of extracellular matrix components  Stephen R. Reeves, MD, PhD, Tessa.
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,
MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,
Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD  Rubaiyat Haque, MBBS,

Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD  Rubaiyat Haque, MBBS,
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.
Regulatory T cells as a biomarker for response to adalimumab in rheumatoid arthritis  Dao X. Nguyen, BSc, Alice Cotton, RN, BSc, Laura Attipoe, MBBS, Coziana.

Regulatory T cells as a biomarker for response to adalimumab in rheumatoid arthritis  Dao X. Nguyen, BSc, Alice Cotton, RN, BSc, Laura Attipoe, MBBS, Coziana.
Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production  Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,

Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production  Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,
Asthma inflammatory phenotypes show differential microRNA expression in sputum  Tania Maes, PhD, Francisco Avila Cobos, MSc, Florence Schleich, MD, PhD,

Asthma inflammatory phenotypes show differential microRNA expression in sputum  Tania Maes, PhD, Francisco Avila Cobos, MSc, Florence Schleich, MD, PhD,
Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated.

Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated.
Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade.

Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade.
CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion  Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion  Theresa Frenz, PhD, Elena Grabski, PhD, Daniela.
IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: Implications for chronic obstructive pulmonary disease 

IL-10 disrupts the Brd4-docking sites to inhibit LPS-induced CXCL8 and TNF-α expression in monocytes: Implications for chronic obstructive pulmonary disease 
Defective nuclear entry of hydrolases prevents neutrophil extracellular trap formation in patients with chronic granulomatous disease  Susana Romao, PhD,

Defective nuclear entry of hydrolases prevents neutrophil extracellular trap formation in patients with chronic granulomatous disease  Susana Romao, PhD,
MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers  Thomas X. Lu,
Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation  Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation  Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,
IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis  Norbert Meyer, MD, Maya Zimmermann, PhD,

IL-32 is expressed by human primary keratinocytes and modulates keratinocyte apoptosis in atopic dermatitis  Norbert Meyer, MD, Maya Zimmermann, PhD,
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,
Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions  Mauro Giacomelli, PhD, Rajesh.

Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions  Mauro Giacomelli, PhD, Rajesh.
Differential control of TH1 versus TH2 cell responses by the combination of low-dose steroids with β2-adrenergic agonists  Elena Goleva, PhD, Annegret.

Differential control of TH1 versus TH2 cell responses by the combination of low-dose steroids with β2-adrenergic agonists  Elena Goleva, PhD, Annegret.

Similar presentations

Ads by Google