Pulmonary Administration of TLR2/6 Agonist after Allergic Sensitization Inhibits Airway Hyper-Responsiveness and Recruits Natural Killer Cells in Lung Parenchyma.

Asthma is a chronic lung disease with persistent airway inflammation, bronchial hyper-reactivity, mucus overproduction, and airway remodeling. Antagonizing T2 responses by triggering the immune system with microbial components such as Toll-like receptors (TLRs) has been suggested as a therapeutic concept for allergic asthma. The aim of this study was to evaluate the effect of a TLR2/6 agonist, FSL-1 (Pam2CGDPKHPKSF), administered by intranasal instillation after an allergic airway reaction was established in the ovalbumin (OVA) mouse model and to analyze the role of natural killer (NK) cells in this effect.

Natural killer cells in the lung: potential role in asthma and virus-induced exacerbation?

Asthma is a chronic inflammatory airway disorder whose pathophysiological and immunological mechanisms are not completely understood. Asthma exacerbations are mostly driven by respiratory viral infections and characterised by worsening of symptoms. Despite current therapies, asthma exacerbations can still be life-threatening.

Platelets Purification Is a Crucial Step for Transcriptomic Analysis.

Platelets are small anucleate cells derived from the fragmentation of megakaryocytes and are involved in different biological processes especially hemostasis, thrombosis, and immune response. Despite their lack of nucleus, platelets contain a reservoir of megakaryocyte-derived RNAs and all the machinery useful for mRNA translation. Interestingly, platelet transcriptome was analyzed in health and diseases and led to the identification of disease-specific molecular signatures.

Platelets: a potential role in chronic respiratory diseases?

Platelets are small anucleate cells known for their role in haemostasis and thrombosis. In recent years, an increasing number of observations have suggested that platelets are also immune cells and key modulators of immunity. They express different receptors and molecules that allow them to respond to pathogens, and to interact with other immune cells.

Regulation of IL (Interleukin)-33 Production in Endothelial Cells via Kinase Activation and Fas/CD95 Upregulation.

Objective: The occurrence of new blood vessel formation in the lungs of asthmatic patients suggests a critical role for airway endothelial cells (ECs) in the disease. IL-33 (Interleukin-33)-a cytokine abundantly expressed in human lung ECs-recently emerged as a key factor in the development of allergic diseases, including asthma. In the present study, we evaluated whether mouse and human ECs exposed to the common allergen produce IL-33 and characterized the activated signaling pathways.

Aberrant anti-viral response of natural killer cells in severe asthma.

Rhinovirus infections are the main cause of asthma exacerbations. As natural killer (NK) cells are important actors of the antiviral innate response, we aimed at evaluating the functions of NK cells from severe asthma patients in response to rhinovirus-like molecules or rhinoviruses.Peripheral blood mononuclear cells from patients with severe asthma and healthy donors were stimulated with pathogen-like molecules or with the rhinoviruses (RV)-A9 and RV-2.

Muc5b-deficient mice develop early histological lung abnormalities.

Gel-forming mucins are the main organic component responsible for physical properties of the mucus hydrogels. While numerous biological functions of these mucins are well documented, specific physiological functions of each mucin are largely unknown. To investigate functions of the gel-forming mucin Muc5b, which is one of the major secreted airway mucins, along with Muc5ac, we generated mice in which Muc5b was disrupted and maintained in the absence of environmental stress.

Endothelial Cell Activation Is Regulated by Epidermal Growth Factor-like Domain 7 (Egfl7) during Inflammation.

Activation of the blood vessel endothelium is a critical step during inflammation. Endothelial cells stimulated by pro-inflammatory cytokines play an essential part in the adhesion and extravasation of circulating leukocytes into inflamed tissues. The endothelial egfl7 gene (VE-statin) represses endothelial cell activation in tumors, and prior observations suggested that it could also participate in the regulation of endothelial cell activation during inflammation.

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

Background: Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR).

Objective: We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity.

The non glycanated endocan polypeptide slows tumor growth by inducing stromal inflammatory reaction.

Endocan expression is increasingly studied in various human cancers. Experimental evidence showed that human endocan, through its glycan chain, is implicated in various processes of tumor growth. We functionally characterize mouse endocan which is also a chondroitin sulfate proteoglycan but much less glycanated than human endocan.

CCL17 production by dendritic cells is required for NOD1-mediated exacerbation of allergic asthma.

Rationale: Pattern recognition receptors are attractive targets for vaccine adjuvants, and polymorphisms of the innate receptor NOD1 have been associated with allergic asthma.

Objectives: To elucidate whether NOD1 agonist may favor allergic asthma in humans through activation of dendritic cells, and to evaluate the mechanisms involved using an in vivo model.

Methods: NOD1-primed dendritic cells from allergic and nonallergic donors were characterized in vitro on their phenotype, cytokine secretion, and Th2 polarizing ability.

The disulfide bond between cysteine 10 and cysteine 34 is required for CCL18 activity.

Asthma is a Th2-mediated disease that involves Th2 cell and eosinophil migration into the bronchial mucosa which is dependent upon the expression of a specific set of chemokines within the lung. Among them, CCL18 seems to play a key role because of its preferential expression in the lung, and its up-regulation by Th2 cytokines. Here, we show that the optimal naïve T cell and basophil chemotaxis, and basophil histamine release induced by rhCCL18 occurred at a 100 time lower concentration with CHO-derived rhCCL18 than with E.

Role of CCL17 in the generation of cutaneous inflammatory reactions in Hu-PBMC-SCID mice grafted with human skin.

CCL17 may be of interest in skin inflammation, because it mainly attracts T cells expressing the cutaneous homing receptor and binds the chemokine receptor CCR4, preferentially expressed on Th-2 cells. We evaluated the in vivo effect of CCL17 injection in a humanized mouse model. (125)I-CCL17 injection into human skin grafted on severe combined immunodeficient (SCID) mice reconstituted with peripheral blood mononuclear cells resulted in a rapid transportation of CCL17 from the skin to the homolateral lymph nodes, followed 3 hours later by a lymph node infiltration of human memory CD4+ cells and dendritic cells.

Toll-like receptor-expressing cells for antiallergy compound screening.

Background: Regulation of type 2 helper T cell (TH2) polarization by toll-like receptors (TLRs) has triggered great interest in new antiallergic therapeutics. In addition to being involved in the regulation of co-stimulation by antigen-presenting cells, they are expressed on other immune and non-immune cells.

Objective: To review the expression and function of TLRs on these cells and their potential to regulate TH2-associated responses.

Impact of lactic Acid bacteria on dendritic cells from allergic patients in an experimental model of intestinal epithelium.

Lactic acid bacteria (LAB) are Gram positive nonpathogenic commensal organisms present in human gastrointestinal tract. In vivo, LAB are separated from antigen-presenting cells such as dendritic cells (DC) by the intestinal epithelial barrier. In this study, the impact of one LAB strain (Lactobacillus casei ATCC393) on human monocyte-derived DC from allergic and healthy donors was assessed by using a polarized epithelium model.

Dendritic cells and toll-like receptors in allergy and asthma.

Epithelia represent a major portal of entry for pathogen microorganisms and allergens and are equipped with innate and adaptive immunity for their protection. Pattern recognition receptors (PRR), including Toll-Like Receptors (TLR), recognize pathogen-associated molecular patterns (PAMP) shared by numerous microorganisms. TLR engagement is involved in innate immunity but also participates in the control of the adaptive immune response, which may be involved in the pathophysiology of allergic diseases like asthma.

In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma.

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell-mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4(+) T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge.

Migration and accumulation of eosinophils toward regional lymph nodes after airway allergen challenge.

Background: Eosinophils play a major role in allergic airway inflammation because of their ability to release toxic mediators. In addition, they are able to migrate toward draining thoracic lymph nodes (TLNs) after intratracheal administration, where they can function as antigen-presenting cells.

Objective: In this study, we evaluated in vivo eosinophil migration toward the TLN after allergen sensitization and analyzed expression of molecules involved in antigen presentation.

Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness.

The effect of modifying early neutrophil-mediated inflammation on the development of airway hyperresponsiveness (AHR) was investigated using an interleukin (IL)-1 receptor antagonist (IL-1Ra), an anti-IL-18 antibody (anti-IL-18) or a p38 mitogen-activated protein kinase (MAPK) inhibitor (M39). Balb/c mice were sensitized to ovalbumin (OVA) and challenged with a single intranasal dose of OVA. Treatment with the IL-1Ra or anti-IL-18 was initiated 20 min before challenge, whereas M39 was administered 4 h before the challenge.

Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function.

The lung collectin surfactant protein D (SP-D) is an important component of the innate immune response but is also believed to play a role in other regulatory aspects of immune and inflammatory responses within the lung. The role of SP-D in the development of allergen-induced airway inflammation and hyperresponsiveness (AHR) is not well defined. SP-D levels progressively increased up to 48 hours after allergen challenge of sensitized mice and then subsequently decreased.

The role of IL-13 in established allergic airway disease.

The effectiveness of targeting IL-13 in models where airway hyperresponsiveness (AHR) and airway inflammation have already been established is not well-described. We investigated the effects of blocking IL-13 on the early and late phase airway responses and the development of AHR in previously sensitized and challenged mice. BALB/cByJ mice were sensitized (days 1 and 14) and challenged (days 28-30) with OVA.

Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness.

Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses. We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guérin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR). Mice were sensitized to OVA by i.