Critical link between glycogen synthase kinase 3β and forkhead box P3 in patients with chronic rhinosinusitis with nasal polyps Xingmei Wu, MD, Sihua.

Slides:

Advertisements

Similar presentations

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Advertisements

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

Alternation of circadian clock modulates forkhead box protein-3 gene transcription in CD4+ T cells in the intestine Gui Yang, MD, Hong Zhang, PhD, Yi.

Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B

Forkhead box protein 3 (FOXP3) mutations lead to increased TH17 cell numbers and regulatory T-cell instability Laura Passerini, PhD, Sven Olek, PhD,

Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3 Feng Lan, MD, Nan Zhang,

Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3 Feng Lan, MD, Nan Zhang,

The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic.

Obstructive sleep apnea syndrome and inflammation

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Alternation of circadian clock modulates forkhead box protein-3 gene transcription in CD4+ T cells in the intestine Gui Yang, MD, Hong Zhang, PhD, Yi.

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis Hyun-Woo Shin, MD, PhD, Dong-Kyu Kim, MD, Min-Hyun Park, MD,

Anju T. Peters, MD, Atsushi Kato, PhD, Ning Zhang, PhD, David B

Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese Ping-Ping Cao, MD, Hua-Bin Li, MD, PhD, Bao-Feng.

Prostaglandin E2 suppresses CCL27 production through EP2 and EP3 receptors in human keratinocytes Naoko Kanda, MD, PhD, Hiroshi Mitsui, MD, PhD, Shinichi.

T-cell regulation during viral and nonviral asthma exacerbations

Chronic rhinosinusitis with polyps and without polyps is associated with increased expression of suppressors of cytokine signaling 1 and 3 Se Jin Park,

Is 9 more than 2 also in allergic airway inflammation?

Suzana Radulovic, MD, Mikila R. Jacobson, PhD, Stephen R

Specificity protein 1 is pivotal in the skin’s antiviral response

Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in patients with chronic rhinosinusitis and their possible contribution to local glucocorticoid.

TNF-α–induced protein 3 (A20): The immunological rheostat

Evidence of a role for B cell–activating factor of the TNF family in the pathogenesis of chronic rhinosinusitis with nasal polyps Atsushi Kato, PhD,

Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing.

Effects of lidocaine on regulatory T cells in atopic dermatitis

T-cell regulation in chronic paranasal sinus disease

Role of TWIK-related potassium channel-1 in chronic rhinosinusitis

Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway Chun-Hua.

Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis Chun Wei Li, PhD, Li Shi, MD, Ke Ke Zhang, MD, Tian.

IL-13 desensitizes β2-adrenergic receptors in human airway epithelial cells through a 15-lipoxygenase/G protein receptor kinase 2 mechanism Giusy D.

Decreased T-cell receptor signaling through CARD11 differentially compromises forkhead box protein 3–positive regulatory versus TH2 effector cells to.

Yuichi Teraki, MD, Aika Sakurai, MD, Seiichi Izaki, MD

Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy Weiping Wen, PhD, Wenlong Liu, MD, Luo Zhang, PhD, Jing Bai,

Forkhead box protein 3 (FOXP3) mutations lead to increased TH17 cell numbers and regulatory T-cell instability Laura Passerini, PhD, Sven Olek, PhD,

Corticosteroid insensitivity of chemokine expression in airway smooth muscle of patients with severe asthma Po-Jui Chang, MD, Pankaj K. Bhavsar, PhD,

RAGE processing in chronic airway conditions: Involvement of Staphylococcus aureus and ECP Koen Van Crombruggen, PhD, Gabriele Holtappels, Natalie De.

Physical exercise modulates the homeostasis of human regulatory T cells Max Weinhold, MA, Alexander Shimabukuro-Vornhagen, MD, Axel Franke, MD, Sebastian.

Bcl2-like protein 12 plays a critical role in development of airway allergy through inducing aberrant TH2 polarization Zhi-Qiang Liu, MD, PhD, Ying Feng,

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses Douglas R. McDonald, MD, PhD,

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA GATA3-AS1 Huan Zhang, MD, PhD, Colm E. Nestor, PhD, Shuli Zhao, PhD,

Fibronectin is a TH1-specific molecule in human subjects

Cigarette smoke combined with Toll-like receptor 3 signaling triggers exaggerated epithelial regulated upon activation, normal T-cell expressed and secreted/CCL5.

David D. Tieu, MD, Anju T. Peters, MD, Roderick T

Effect of budesonide transnasal nebulization in patients with eosinophilic chronic rhinosinusitis with nasal polyps Chengshuo Wang, MD, Hongfei Lou,

Possible role of TH17 cells in the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis Yuichi Teraki, MD, Misaki Kawabe, MD, Seiichi.

A lower prevalence of asthma among patients with chronic rhinosinusitis in southern China Yunping Fan, MD, PhD, Shuli Chen, MD, PhD, Xiujuan Qu, MD,

Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis Deepti R. Nagarkar, PhD, Julie A. Poposki,

The Editors' Choice Journal of Allergy and Clinical Immunology

Fibronectin is a TH1-specific molecule in human subjects

Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response

IκB kinase–driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease Rosalia Gagliardo, PhD, Pascal Chanez,

The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity

Liam O’Mahony, PhD, Mübeccel Akdis, MD, PhD, Cezmi A. Akdis, MD

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis Hyun-Woo Shin, MD, PhD, Dong-Kyu Kim, MD, Min-Hyun Park, MD,

Autophagy: Nobel Prize 2016 and allergy and asthma research

Lei Wang, MD, PhD, Jesse P. Joad, MD, Caiyun Zhong, MD, PhD, Kent E

Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease Nan Zhang, MD, PhD, Thibaut Van Zele, MD, PhD, Claudina.

Influence of cytomegalovirus infection on immune cell phenotypes in patients with common variable immunodeficiency Sayed Mahdi Marashi, PhD, Mohammed.

The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis Meiqin Wang, MD, PhD, Julita Ramirez, DVM, PhD,

Katie Frith, MD, Anne-Laure Joly, PhD, Cindy S. Ma, PhD, Stuart G

Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps Joke Patou, MD, Philippe Gevaert, MD, PhD, Thibaut.

Wasp venom immunotherapy expands a subpopulation of CD4+CD25+ forkhead box protein 3–positive regulatory T cells expressing the T-cell receptor Vβ2 and.

Inflammation-mediated upregulation of centrosomal protein 110, a negative modulator of ciliogenesis, in patients with chronic rhinosinusitis Yinyan Lai,

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis Jennifer K. Mulligan, PhD, Whitney Nagel,

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis Wenlong Liu, MD, Wentong.

Chitinases and chitinase-like proteins in TH2 inflammation and asthma

CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell deficiencies Xiaowen Wang, MD, Wenyan Wang, PhD, Zhimiao Lin, MD, Xiaolin Wang,

Der p 1–induced CD4+FOXP3+GATA3+ T cells have suppressive properties and contribute to the polarization of the TH2-associated response Lieke Reubsaet,

Presentation transcript:

Critical link between glycogen synthase kinase 3β and forkhead box P3 in patients with chronic rhinosinusitis with nasal polyps Xingmei Wu, MD, Sihua Wang, PhD, Miaomiao Han, PhD, Bin Song, PhD, Ping Ye, MD, Shanshan Ma, MD, Jun Li, MD, Fenghong Chen, MD, Geng Xu, PhD, Qingqing Ding, PhD, Jiahong Xia, PhD, Huabin Li, PhD Journal of Allergy and Clinical Immunology Volume 136, Issue 6, Pages 1698-1700.e12 (December 2015) DOI: 10.1016/j.jaci.2015.08.014 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Expression of GSK-3β and Foxp3 in sinonasal tissues. A, Immunoreactivity of GSK-3β in sinonasal tissues (magnification ×200). B, Mean number of GSK-3β+ cells in sinonasal tissues. C and D, mRNA level of GSK-3β and Foxp3 in sinonasal tissues. E, Representative Western blot results of GSK-3β and Foxp3 protein expression in sinonasal tissues. F, Relative protein levels of GSK-3β and Foxp3 in NP tissues. G, Representative western blot results of p-Foxp3 (Ser 270) in NP tissues and UTs. H, Relative protein level of p-Foxp3 in NP tissues compared with UTs. NS, No significance. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 mRNA expression of TH cell subsets in sinonasal tissues of patients with CRSwNP. mRNA levels of T-box transcription factor (T-bet; A), GATA-3 (B), and retinoic acid–related orphan receptor C (RORc; C) in NP tissues were significantly increased compared with those in UTs of patients with CRSwNP (n = 22). **P < .01. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 mRNA expression of inflammatory cytokines in sinonasal tissues of patients with CRSwNP. mRNA levels of TNF-α (A), IL-1β (B), IFN-γ (C), IL-4 (D), IL-5 (E), IL-13 (F), IL-6 (G), IL-17A (H), and IL-22 (I) in NP tissues were significantly increased compared with those in UTs in patients with CRSwNP (n = 22) are shown. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Expression of Foxp3 in sinonasal tissues of patients with CRSwNP. A, Immunoreactivity of Foxp3 in NP tissues and UTs of patients with CRSwNP and tonsils of healthy control subjects (as a positive control, magnification ×200). B, Mean number of Foxp3+ cells was significantly decreased in NP tissues compared with UTs. **P < .01. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Relative protein levels of GSK-3β and Foxp3 in sinonasal tissues of patients with CRSwNP. A, Relative protein levels of GSK-3β were significantly increased in NP tissues compared with those in 3 other healthy UT groups. B, Relative protein levels of Foxp3 were significantly decreased in NP tissues compared with those in the other 3 healthy UT groups (n = 14). **P < .01. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Ratio of Foxp3+CD4+ cells in sinonasal tissues. A, Representative flow cytometric results of Foxp3+CD4+ cells in NP tissues and UTs of patients with CRSwNP. B, Frequencies of Foxp3+CD4+ cells were significantly decreased in NP tissues compared with those in UTs. **P < .01. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Colocalization of GSK-3β and Foxp3 protein in Treg cells. Representative flow cytometric results of GSK-3β+ Treg cells (Foxp3+CD4+) in NP tissues of patients with CRSwNP, as well as in PBMCs and tonsils of healthy control subjects, were shown. MFI, Mean fluorescence index. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E7 Interaction of GSK-3β and Foxp3 protein in vitro. A, GSK-3β physically interacts with Foxp3. B, GSK-3β promotes the instability of the Foxp3 protein level. Inhibition of GSK-3β with specific siRNA significantly prolonged the half-life of Foxp3 protein in HEK 293T cells. C, GSK-3β modulates Foxp3 protein levels. IP, Immunoprecipitation. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E8 GSK-3β phosphorylates Foxp3 by targeting a motif of Ser 270/274. A, GSK-3β phosphorylates Foxp3. B, Mass spectrometric analysis revealed that a motif in Foxp3 between residues 270 and 275 can be phosphorylated by GSK-3β. C, GSK-3β phosphorylated Ser 270/274 in Foxp3 protein in vitro. D, Mutated Ser 270/274 cannot be phosphorylated in vivo. FLAG-Foxp3 wild-type or mutant A (270/274) or B (271/275) was transfected in HEK 293T cells. E, GSK-3β phosphorylated Ser 270/274 in Foxp3 protein in vivo. Journal of Allergy and Clinical Immunology 2015 136, 1698-1700.e12DOI: (10.1016/j.jaci.2015.08.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions