CCL17 Production by Dendritic Cells Is Required for NOD1-mediated Exacerbation of Allergic Asthma

Yahia, Saliha Ait; Azzaoui, Imane; Everaere, Laëtitia; Vorng, Han; Chenivesse, Cécile; Marquillies, Philippe; Duez, Catherine; Delacre, Myriam; Grandjean, Teddy; Balsamelli, Joanne; d'Andon, Martine Fanton; Fan, Ying; Plé, Coline; Werts, Catherine; Boneca, Ivo Gomperts; Wallaert, B.; Chamaillard, Mathias; Tsicopoulos, Anne

doi:10.1164/rccm.201310-1827oc

Cited by 29 publications

(31 citation statements)

References 42 publications

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“…Pulmonary DCs were also highly elevated in Tlr4 -mutant mice in an allergic inflammation model, which supports our study, as well as several inflammatory markers typically increased by activated DCs in lungs of BALB Lspd mice treated with BHT, such as costimulatory molecule (CD40, data not shown) and Ccl17 (Tarc) (Fig 7) (42, 54, 55). The DCs can also lead to NK cell activation, which we observed increased cell numbers, with potential to secrete cytokines/chemokines that activate specific types of macrophages (e.g.…”

Section: Discussionsupporting

confidence: 88%

“…At sacrifice, lungs were ½ lung bronchoalveolar lavaged (42) with Hanks Balanced Salt Solution (HBSS) with ethylenediaminetetraacetic disodium salt (EDTA) to determine immune cell constituents using cellular differentials in the BAL fluid (BALF), as done previously (29). For flow cytometry, the lavaged right lung was minced and digested with 1 mg/ml collagenase (43) at 37°C for 30 min (44).…”

Section: Methodsmentioning

confidence: 99%

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Differential innate immune cell signatures and effects regulated by toll-like receptor 4 during murine lung tumor promotion

Alexander

Xiong

Velmurugan

et al. 2016

Experimental Lung Research

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Tumor promotion is an early and critical stage during lung adenocarcinoma (ADC). We previously demonstrated that Tlr4 mutant mice were more susceptible to butylated hydroxytoluene (BHT)-induced pulmonary inflammation and tumor promotion in comparison to Tlr4-sufficient mice. Our study objective was to elucidate the underlying differences in Tlr4 mutant mice in innate immune cell populations, their functional responses, and the influence of these cellular differences on ADC progenitor (type II) cells following BHT-treatment. BALB (Tlr4-sufficient) and C.C3-Tlr4Lps-d/J (BALBLpsd; Tlr4 mutant) mice were treated with BHT (promoter) followed by bronchoalveolar lavage (BAL) and flow cytometry processing on the lungs. ELISAs, Club cell enrichment, macrophage function and RNA isolation were also performed. Bone marrow-derived macrophages (BMDM) co-cultured with a type II cell line were used for wound healing assays. Innate immune cells significantly increased in whole lung in BHT treated BALBLpsd mice compared to BALB mice. BHT treated BALBLpsd mice demonstrated enhanced macrophage functionality, increased epithelial wound closure via BMDMs, and increased Club cell number in BALBLpsd mice, all compared to BALB BHT-treated mice. Cytokine/chemokine (Kc, Mcp1) and growth factor (Igf1) levels also significantly differed among the strains and within macrophages, gene expression and cell surface markers collectively demonstrated a more plastic phenotype in BALBLpsd mice. Therefore, these correlative studies suggest that distinct innate immune cell populations are associated with the differences observed in the Tlr4-mutant model. Future studies will investigate the macrophage origins and the utility of the pathways identified herein as indicators of immune system deficiencies and lung tumorigenesis.

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Section: Discussionsupporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Differential innate immune cell signatures and effects regulated by toll-like receptor 4 during murine lung tumor promotion

Alexander

Xiong

Velmurugan

et al. 2016

Experimental Lung Research

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“…21,34 CCL17 was not only released from DCs but also promoted the maturation of DCs via a positive feedback to enhance the polarization of Th2 cells. 35,36 Knock-down of CCL17 during the maturation of DCs decreased the recruitment of CD4 + T cells and Tregs. 37 Reports showed that the interaction of RSV and Th2 cytokines tends to induce the expression of CCL17 via NF-κB and STAT6 pathway respectively.…”

Section: Discussionmentioning

confidence: 99%

Targeting TSLP With shRNA Alleviates Airway Inflammation and Decreases Epithelial CCL17 in a Murine Model of Asthma

Chen

Chiang

2016

Molecular Therapy - Nucleic Acids

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Airway epithelium defends the invasion from microorganisms and regulates immune responses in allergic asthma. Thymic stromal lymphopoietin (TSLP) from inflamed epithelium promotes maturation of dendritic cells (DCs) to prime Th2 responses via CCL17, which induces chemotaxis of CD4+ T cells to mediate inflammation. However, few studies have investigated the regulation of epithelial CCL17. In this study, we used shRNA against TSLP to clarify the role of TSLP in the airway inflammation and whether TSLP affects the airway inflammation via epithelial CCL17. Specific shTSLP was delivered by lentivirus and selected by the knockdown efficiency. Allergic mice were intratracheally pretreated with the lentivirus and followed by intranasal ovalbumin (OVA) challenges. The sera antibody levels, airway inflammation, airway hyper-responsiveness (AHR), cytokine levels in bronchoalveolar lavage fluids, and CCL17 expressions in lungs were determined. In vivo, TSLP attenuation reduced the AHR, decreased the airway inflammation, inhibited the maturations of DCs, and suppressed the migration of T cells. Furthermore, the expression of CCL17 was particularly decreased in bronchial epithelium. In vitro, CCL17 induction was regulated by TSLP. In conclusion, TSLP might coordinate airway inflammation partially via CCL17-mediated responses and this study provides the vital utility of TSLP to develop the therapeutic approach in allergic airway inflammation.

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“…NOD1-primed human DCs polarize naive T cells toward a Th2 profile, favoring allergic exacerbations, and this is due to the induction of CCL17 (chemokine pro-Th2). Vaccine formulations that engage NOD1 could contribute to increasing allergic asthma [100] …”

Section: Immunology and Lung Diseasesmentioning

confidence: 99%

Immune Recognition in Lung Diseases: Basic Research and Clinical Application

Alvarado¹,

Arce²

2016

Clin Infect Immun

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Respiratory diseases are among the leading causes of morbidity and mortality in the world population. Our understanding of the molecular mechanisms leading to recognition of infectious pathogens and harmful endogenous signals by the innate immune system and the adaptive immune system has improved significantly in recent decades. There is increased evidence of the key role of the immune system with its pattern recognition receptors (PRRs) in infectious and non-infectious lung diseases. The PRRs are a family of sensors able to sense different microbial molecules as well as endogenous molecules which are released by the host tissue damage. The commitment of PRRs is a prerequisite for the initiation of immune and inflammatory response to infection and tissue injury that may be beneficial or harmful. The PRRs are germ-line encoded, evolutionarily conserved molecules and consist of Toll-like receptors, NOD-like receptors, RIG-I-like receptors, C-type lectin-like receptors and cytosolic DNA sensors. This review summarizes the prominent role of transmembrane and cytosolic PRRs in the pathogenesis of infectious and non-infectious lung diseases. The PRRs and their signals represent promising targets for prophylactic and therapeutic strategies in various lung diseases.

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CCL17 Production by Dendritic Cells Is Required for NOD1-mediated Exacerbation of Allergic Asthma

Abstract: Data from this study unveil a deleterious role of NOD1 in allergic asthma through direct induction of CCL17 by dendritic cells, arguing for a need to address vaccine formulation safety issues related to allergy.

Cited by 29 publications

References 42 publications

Differential innate immune cell signatures and effects regulated by toll-like receptor 4 during murine lung tumor promotion

Differential innate immune cell signatures and effects regulated by toll-like receptor 4 during murine lung tumor promotion

Targeting TSLP With shRNA Alleviates Airway Inflammation and Decreases Epithelial CCL17 in a Murine Model of Asthma

Immune Recognition in Lung Diseases: Basic Research and Clinical Application

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