Induced CD4+ forkhead box protein–positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1 Wenru Su, MD, Huimin.

Slides:

Advertisements

Similar presentations

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.

Advertisements

Volume 144, Issue 3, Pages e1 (March 2013)

Therapeutic reversal of food allergen sensitivity by mature retinoic acid–differentiated dendritic cell induction of LAG3+CD49b−Foxp3− regulatory T cells

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy Yin Yao, MD, Cai-Ling.

William A. Comrie, PhD, Aiman J

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.

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven TH1 differentiation Regina K. Rowe, MD, PhD, David M. Pyle, MD,

The sphingosine-1-phosphate/sphingosine-1-phosphate receptor 2 axis regulates early airway T-cell infiltration in murine mast cell–dependent acute allergic.

Insulin-like growth factor 2 enhances regulatory T-cell functions and suppresses food allergy in an experimental model Gui Yang, MD, Xiao-Rui Geng, MD,

Rapamycin preferentially inhibits human IL-5+ TH2-cell proliferation via an mTORC1/S6 kinase-1–dependent pathway Yuzhi Yin, MD, PhD, Alyssa Mitson-Salazar,

Targeting Toll-like receptors on dendritic cells modifies the TH2 response to peanut allergens in vitro Pierre Pochard, PhD, Brian Vickery, MD, M. Cecilia.

Autocrine hemokinin-1 functions as an endogenous adjuvant for IgE-mediated mast cell inflammatory responses Tina L. Sumpter, PhD, Chin H. Ho, MD, Anna.

IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs Chien-Chang Chen, PhD, Takao Kobayashi, PhD, Koji Iijima,

Naive T cells sense the cysteine protease allergen papain through protease-activated receptor 2 and propel TH2 immunity Genqing Liang, PhD, Tolga Barker,

Efficient cytokine-induced IL-13 production by mast cells requires both IL-33 and IL-3 Ilkka S. Junttila, MD, PhD, Cynthia Watson, BSc, Laura Kummola,

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

Lung dendritic cells induce TH17 cells that produce TH2 cytokines, express GATA-3, and promote airway inflammation Marianne Raymond, PhD, Vu Quang Van,

Activated glycoprotein A repetitions predominant (GARP)–expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice

Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A.

Glucocorticoids promote intrinsic human TH17 differentiation

Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy Maryam Hussain, MSc, Loïc Borcard,

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice László Hortobágyi, MS, Sonja Kierstein, PhD, Kateryna Krytska,

Dawn C. Newcomb, PhD, Madison G

Α-MSH-Stimulated Tolerogenic Dendritic Cells Induce Functional Regulatory T Cells and Ameliorate Ongoing Skin Inflammation Matteo Auriemma, Thomas Brzoska,

Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator–inducible T-cell.

Pharmacologic inhibition of Notch signaling suppresses food antigen–induced mucosal mast cell hyperplasia Asuka Honjo, MD, Nobuhiro Nakano, PhD, Susumu.

CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling Jennifer Kearley, PhD, Douglas S. Robinson,

Forkhead box protein 3 demethylation is associated with tolerance induction in peanut- induced intestinal allergy Meiqin Wang, MD, PhD, Ivana V. Yang,

Oliver T. Burton, PhD, Jaciel M. Tamayo, PhD, Amanda J

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

Culture medium from TNF-α–stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms Wenru Su, MD,

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

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

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

David M. Pyle, BS, Victoria S. Yang, MD, Rebecca S

Capsiate Inhibits DNFB-Induced Atopic Dermatitis in NC/Nga Mice through Mast Cell and CD4+ T-Cell Inactivation Ji H. Lee, Yun S. Lee, Eun-Jung Lee, Ji.

Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype Nicolas Gaudenzio, PhD, Camille Laurent, MD, Salvatore Valitutti,

Prostaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells Zbigniew Zasłona, PhD, Katsuhide.

Takao Kobayashi, PhD, Koji Iijima, PhD, Alexander L

Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8+ T cells Kamal D. Srivastava,

Janus kinase 1/3 signaling pathways are key initiators of TH2 differentiation and lung allergic responses Shigeru Ashino, PhD, Katsuyuki Takeda, MD,

Dysregulation of proinflammatory versus anti-inflammatory human TH17 cell functionalities in the autoinflammatory Schnitzler syndrome Rebecca Noster,

3-Methyl-4-nitrophenol triggers nasal allergy by modulating dendritic cell properties Xiao-Yu Liu, PhD, Yong-Jin Wu, MD, PhD, Li-Juan Song, MD, Xian-Hai.

Estrogen increases the severity of anaphylaxis in female mice through enhanced endothelial nitric oxide synthase expression and nitric oxide production

Fibronectin is a TH1-specific molecule in human subjects

Dichotomy of short and long thymic stromal lymphopoietin isoforms in inflammatory disorders of the bowel and skin Giulia Fornasa, PhD, Katerina Tsilingiri,

Docosahexaenoic Acid Alleviates Atopic Dermatitis by Generating Tregs and IL-10/TGF- β-Modified Macrophages via a TGF-β-Dependent Mechanism Sang-Chul.

Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)–1/TIM4 interaction as a therapeutic strategy in a dendritic cell–induced peanut allergy.

Zoulfia Allakhverdi, PhD, Michael R. Comeau, BSc, Dirk E

Bet v 1–specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1–specific T-cell effector function in an activation-dependent.

Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy Maryam Hussain, MSc, Loïc Borcard,

Volume 24, Issue 2, Pages (February 2006)

Antigen-Presenting Cell Production of IL-10 Inhibits T-Helper 1 and 17 Cell Responses and Suppresses Colitis in Mice Bo Liu, Susan L. Tonkonogy, R. Balfour.

Prostaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells Zbigniew Zasłona, PhD, Katsuhide.

Role of B cells in TH cell responses in a mouse model of asthma

Airway epithelial cells activate TH2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin Deepti R. Nagarkar, PhD, Julie A.

Sarita Sehra, PhD, Weiguo Yao, PhD, Evelyn T. Nguyen, MS, Nicole L

Fibronectin is a TH1-specific molecule in human subjects

Volume 48, Issue 4, Pages e6 (April 2018)

Notch signaling confers antigen-presenting cell functions on mast cells Nobuhiro Nakano, PhD, Chiharu Nishiyama, PhD, Hideo Yagita, PhD, Akemi Koyanagi,

The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells Juha Punnonen, MD, PhD, Hans Yssel, PhD,

Volume 35, Issue 2, Pages (August 2011)

Allergen-specific sublingual immunotherapy is dose and duration dependent in a murine allergic rhinitis model Soichi Tofukuji, PhD, Kazufumi Katayama,

Volume 29, Issue 5, Pages (November 2008)

DJ-1 regulates mast cell activation and IgE-mediated allergic responses Do Kyun Kim, PhD, Hyuk Soon Kim, MS, A-Ram Kim, MS, Ji Hyung Kim, BS, Bokyung.

Volume 28, Issue 5, Pages (May 2008)

Harald Renz, MD, Chaya Brodie, PhD, Katherine Bradley, BS, Donald Y. M

Duy Pham, PhD, Sarita Sehra, PhD, Xin Sun, PhD, Mark H. Kaplan, PhD

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

CCL17/thymus and activation-regulated chemokine induces calcitonin gene–related peptide in human airway epithelial cells through CCR4 Kandace Bonner,

Presentation transcript:

Induced CD4+ forkhead box protein–positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1 Wenru Su, MD, Huimin Fan, MD, PhD, Maogen Chen, MD, Julie Wang, BS, David Brand, PhD, Xiaoshun He, MD, PhD, Valerie Quesniaux, PhD, Bernhard Ryffel, MD, PhD, Ling Zhu, PhD, Dan Liang, MD, PhD, Song Guo Zheng, MD, PhD Journal of Allergy and Clinical Immunology Volume 130, Issue 2, Pages 444-452.e7 (August 2012) DOI: 10.1016/j.jaci.2012.05.011 Copyright © 2012 Terms and Conditions

Fig 1 iTreg cells inhibit proinflammatory cytokines released by MCs activated in an IgE-independent manner. BMMCs were cocultured with different CD4+ T cells at the indicated ratios for 24 hours. After stimulation with PMACI for 6 to 16 hours, TNF-α and IL-6 levels in the supernatants were determined by using ELISA (A and B), and the expression of TNF-α and IL-6 mRNA in BMMCs was determined by using real-time PCR (C-F). Values are presented as means ± SEMs of 3 replicates, and experiments were repeated at least 2 times with similar results. **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig 2 iTreg cells inhibit proinflammatory cytokines released by MCs by modulating NF-κB signaling. BMMCs were cocultured with iTreg cells at a 2:1 ratio for 24 hours. After stimulation with PMACI for 16 hours, MCs were isolated from cocultures by using negative selection through autoMACS. The expression of phosphorylated IκB-α (A) and NF-κB p65 (B) in BMMCs was determined by means of Western blotting. Values are presented as means ± SEMs of 3 replicates, and experiments were repeated at least 2 times with similar results. **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig 3 Membrane-bound TGF-β1 is essential for iTreg cell–mediated inhibition on MCs. BMMCs were cultured with or without iTreg cells for 24 hours either under direct cell-cell contact or in a transwell system (A); in the presence or absence of specific neutralizing antibodies for TGF-β1, OX40L, or isotype control IgGs or gap-junction inhibitor (B); or after pretreatment with TGF-β1 siRNA or control siRNA (CSiRNA; C) or SMAD3 inhibitor (D and E) after stimulation with PMACI. TNF-α and IL-6 levels were determined by using ELISA (Fig 3, A-E), and the SMAD3 expression in BMMCs was determined by means of Western blotting (F). Values are presented as means ± SEMs of 3 replicates, and experiments were repeated at least 2 times with similar results. **P < .01. CsiRNA, Blank control siRNA; Isotype, IgG isotype control for anti-OX40L or anti–TGF-β1. a-SMAD3, SMAD3 inhibitor (SIS3). Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig 4 Human iTreg cells suppress proinflammatory cytokine production by a human MC line. HMC-1 cells were cultured with or without different CD4+ T cells, followed by stimulation with PMACI for 6 to 16 hours. TNF-α (A) and IL-6 (B) levels were measured by means of ELISA, and NF-κBp65 (C), TNF-α (D), and IL-6 (E) expression in BMMCs was determined by using Western blotting and real-time PCR, respectively. Values are presented as means ± SEMs of 3 replicates, and experiments were repeated at least 2 times with similar results. **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig 5 iTreg cell treatment attenuates CHS. A, Experimental protocol. B, Ear thickness was measured at indicated time points after challenge in different experimental groups. C, Representative images of hematoxylin and eosin staining of ear samples in normal mice, mice with CHS, and mice with CHS after treatment with iTreg cells. D and E, Quantification of cellular components in ears of mice with CHS and draining lymph nodes. F, Gross draining lymph node weight. Each group includes 5 mice, and experiments were repeated once. The data are either representative or means ± SEMs of 2 separate experiments. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig 6 iTreg cell treatment suppresses MCs in mice with CHS. iTreg cells were transferred to mice with CHS. A, Representative images. MCs were determined by using toluidine blue staining, and activated MCs were identified based on their irregular shape (red arrows) in ears of normal mice, mice with CHS, and iTreg cell–treated mice with CHS, as indicated. B and C, TNF-α and IL-6 mRNA expression determined based on real-time PCR. D, NF-κB expression determined by means of Western blotting. E and F, TGF-β1 mRNA (Fig 6, E) and protein (Fig 6, F) levels determined based on real-time PCR and ELISA. Each group includes 5 mice, and experiments were repeated once. Values are presented as means ± SEMs of 3 replicates. **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig 7 iTreg cell treatment attenuates CHS through TGF-β1. CHS was induced as above, and iTreg cells, either TGF-β1 or control knockdown iTreg cells, were adoptively transferred to mice with CHS. Ear thickness (A), frequency of MCs and numbers of irregular MCs (B), and TNF-α and IL-6 mRNA expression on ear tissues (C) were measured as above at the indicated time points after challenge. Each group includes 5 mice, and experiments were repeated once. Values are presented as means ± SEMs of 2 separate experiments or 3 replicates. **P < .01. ciTreg, iTreg cells treated with blank control siRNA; diTreg, iTreg cells treated with TGF-β1 siRNA. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig E1 TGF-β–induced iTreg cells have a similar ability to express Foxp3 and develop the suppressive activity as nTreg cells. A, Splenic naive CD4+CD25−CD62L+CD44low cells from BALB/C mice were stimulated with anti-CD3/CD28–coated beads (1:5) in the presence of IL-2 (50 U/mL) and TGF-β (2 ng/mL) for 4 days. Splenic nTreg cells sorted from the thymus were stimulated with anti-CD3/CD28–coated beads (1:3) in the presence of IL-2 (300 U/mL) for 7 days. A, The cells were collected for intracellular Foxp3 staining. Scatter plots were gated on CD4 and are representative of 4 separate experiments. B, Carboxyfluorescein succinimidyl ester (CFSE)–labeled effector T cells stimulated with anti-CD3 in the presence of antigen-presenting cells were cultured at a 1:4 ratio with TGF-β–induced Treg or nTreg cells or without (Baseline) for 3 days. Representative CFSE plots of the T effector cells from 4 independent experiments are shown. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig E2 iTreg cells modulate IL-6 production by MCs through TGF-β1 signal. BMMCs were cultured with or without iTreg cells for 24 hours under direct cell-cell contact or in a transwell system (A), in the presence or absence of anti–TGF-β1 and anti-OX40L antibodies or matched isytope control IgG and specific inhibitors for gap junction (B), or after pretreatment with TGF-β1 siRNA or control siRNA (CsiRNA; C). After stimulation with PMACI, IL-6 levels were determined by means of ELISA. Values are presented as means ± SEMs of 3 separate experiments. **P < .01. CsiRNA, Blank control siRNA; Isotype, IgG isotype control for anti-OX40L or anti–TGF-β. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig E3 iTreg cells inhibit the degranulation of MCs activated in an IgE-dependent manner. Anti–DNP-IgE–presensitized BMMCs were challenged with DNP-BSA for 30 minutes in the presence or absence of equal amounts of Treg cells or T control cells. Degranulation was determined by measuring the activity of the MC granule–associated enzyme β-hexosaminidase. Values are presented as means ± SEMs of 3 separate experiments. **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig E4 Differential therapeutic effects of systemic administration of T-cell subsets. iTreg, nTreg, or T control cells were adoptively transferred into mice with CHS, as described in Fig 5, and ear thickness was measured at the time points as indicated after allergen challenge. *P < .05 and **P < .01 in contrast to T control cells transferred to mice with CHS by means of 1-way ANOVA. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig E5 iTreg cell treatment inhibits the production of inflammatory cytokines in the ears of mice with CHS. iTreg cells were transferred to mice with CHS, as described in Fig 6. TNF-α (A), IL-6 (B), and IL-9 (C) production in the supernatants was determined by means of ELISA. Values are presented as means ± SEMs of 3 independent experiments. **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions

Fig E6 Knockdown of TGF-β1 in iTreg cells by siRNA significantly decreases their inhibitory capability on inflammatory cytokine production in mice with CHS. The experiment was conducted similarly to Fig 7. TNF-α and IL-6 production was determined by means of ELISA. Values are presented as means ± SEMs of 3 independent experiments. **P < 0. ciTreg, iTreg cells treated with blank control siRNA; diTreg, iTreg cells treated with TGF-β1 siRNA. Journal of Allergy and Clinical Immunology 2012 130, 444-452.e7DOI: (10.1016/j.jaci.2012.05.011) Copyright © 2012 Terms and Conditions