Bitter taste receptor T2R14-Gαi coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease characterized by microbial infection and progressive decline in lung function, leading to significant morbidity and mortality. The bitter taste receptor T2R14 is a chemosensory receptor that is significantly expressed in airways. Using a combination of cell-based assays and T2R14 knockdown in bronchial epithelial cells from CF and non-CF individuals, we observed that T2R14 plays a crucial role in the detection of bacterial and fungal signals and enhances host innate immune responses.

Expression of Semaphorin3E/PlexinD1 in human airway smooth muscle cells of patients with COPD.

Semaphorin3E (Sema3E) is a member of axon guidance proteins that have emerged recently as essential regulators of cell migration and proliferation. It binds to PlexinD1 with high affinity and is expressed in different cell types, including immune, cancer, and epithelial cells. Recent work in our lab has revealed a critical immunoregulatory role of Sema3E in experimental allergic asthma; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear.

Targeting the Semaphorin3E-plexinD1 complex in allergic asthma.

Asthma is a heterogenous airway disease characterized by airway inflammation and remodeling. It affects more than 300 million people worldwide and poses a significant burden on society. Semaphorins, discovered initially as neural guidance molecules, are ubiquitously expressed in various organs and regulate multiple signaling pathways.

Exogenous Semaphorin 3E treatment protects against chlamydial lung infection in mice.

Recent studies reported that semaphorins play a significant role in various settings of the immune response. In particular, Semaphorin 3E (Sema3E), a secreted semaphorin protein, is involved in cell proliferation, migration, inflammatory responses, and host defence against infections. However, the therapeutic function of Sema3E in bacterial infection has not been investigated.

New Insights on the Role of pentraxin-3 in Allergic Asthma.

Pentraxins are soluble pattern recognition receptors that play a major role in regulating innate immune responses. Through their interaction with complement components, Fcγ receptors, and different microbial moieties, Pentraxins cause an amplification of the inflammatory response. Pentraxin-3 is of particular interest since it was identified as a biomarker for several immune-pathological diseases.

PlexinD1 Deficiency in Lung Interstitial Macrophages Exacerbates House Dust Mite-Induced Allergic Asthma.

Interstitial macrophages (IMs) are key regulators of allergic inflammation. We previously showed that the absence of semaphorin 3E (Sema3E) exacerbates asthma features in both acute and chronic asthma models. However, it has not been studied whether Sema3E, via its receptor plexinD1, regulates IM function in allergic asthma.

Role of CCR3 in respiratory syncytial virus infection of airway epithelial cells.

Respiratory syncytial virus () infection is the principal cause of severe lower respiratory tract disease and accounts for a significant risk for developing asthma later in life. Clinical studies have shown an increase in airway responsiveness and a concomitant Th response in the lungs of RSV-infected patients. These indications suggest that RSV may modulate aspects of the immune response to promote virus replication.

PTX3 Deficiency Promotes Enhanced Accumulation and Function of CD11cCD11b DCs in a Murine Model of Allergic Inflammation.

PTX3 is a unique member of the long pentraxins family and plays an indispensable role in regulating the immune system. We previously showed that PTX3 deletion aggravates allergic inflammation a Th17 -dominant phenotype and enhanced CD4 T cell survival using a murine model of ovalbumin (OVA) induced allergic inflammation. In this study, we identified that upon OVA exposure, increased infiltration of CD11cCD11b dendritic cells (DCs) was observed in the lungs of mice compared to wild type littermate.

Semaphorin 3E deficiency dysregulates dendritic cell functions: In vitro and in vivo evidence.

Regulation of dendritic cell functions is a complex process in which several mediators play diverse roles as a network in a context-dependent manner. The precise mechanisms underlying dendritic cell functions have remained to be addressed. Semaphorins play crucial roles in regulation of various cell functions.

Semaphorin3E/plexinD1 Axis in Asthma: What We Know So Far!

Semaphorin3E belongs to the large family of semaphorin proteins. Semaphorin3E was initially identified as axon guidance cues in the neural system. It is universally expressed beyond the nervous system and contributes to regulating essential cell functions such as cell migration, proliferation, and adhesion.

Semaphorin 3E Protects against Chlamydial Infection by Modulating Dendritic Cell Functions.

Recent studies have identified semaphorin 3E (Sema3E) as a novel mediator of immune responses. However, its function in immunity to infection has yet to be investigated. Using a mouse model of chlamydial lung infection, we show that Sema3E plays a significant role in the host immune response to the infection.

Semaphorin 3E Promotes Susceptibility to Infection in Mice by Suppressing CD4 Th1 Cell Response.

Protective immunity to cutaneous leishmaniasis is mediated by IFN-γ-secreting CD4 Th1 cells. IFN-γ binds to its receptor on -infected macrophages, resulting in their activation, production of NO, and subsequent destruction of parasites. This study investigated the role of Semaphorin 3E (Sema3E) in host immunity to infection in mice.

Semaphorin 3E Regulates the Response of Macrophages to Lipopolysaccharide-Induced Systemic Inflammation.

Semaphorin 3E (Sema3E) is a secreted protein that was initially discovered as a neuronal guidance cue. Recent evidence showed that Sema3E plays an essential role in regulating the activities of various immune cells. However, the exact role of Sema3E in macrophage function, particularly during inflammation, is not fully understood.

Glucocorticoids regulate pentraxin-3 expression in human airway smooth muscle cells.

Pentraxin-3 (PTX3) is a multifunctional protein involved in both innate and adaptive immunity. Glucocorticoid (GC) is the first-line therapy to mitigate airway inflammation in asthma. Previous pieces of evidence showed that GC has divergent effects on PTX3 production in various cell types.

Semaphorin 3E regulates apoptosis in the intestinal epithelium during the development of colitis.

Semaphorin 3E (SEMA3E) has emerged as an axon-guiding molecule that regulates various biological processes including the immune responses and apoptosis. However, its role in the pathophysiology of colitis remains elusive. We investigated the role of SEMA3E in intestinal epithelial cells (IECs) activation, using biopsies from patients with active ulcerative colitis (UC), a mouse model of UC, and an in-vitro model of intestinal mucosal healing.

Semaphorin 3E Inhibits House Dust Mite-Induced Angiogenesis in a Mouse Model of Allergic Asthma.

Increased angiogenesis is a characteristic feature of remodeling in asthmatic airways and stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. Previously, we showed an important role of semaphorins 3E (Sema3E) in growth factor-induced airway smooth muscle proliferation and migration in vitro, and in down-regulating airway inflammation, T helper 2/T helper 17 cytokine response, mucus cell hyperplasia, and airway hyperresponsiveness in vivo.

The regulatory role of semaphorin 3E in allergic asthma.

Semaphorins were originally discovered as essential mediators involved in regulation of axonal growth during development of the nervous system. Ubiquitously expressed on various organs, they control several cellular functions by regulating essential signaling pathways. Among them, semaphorin3E binds plexinD1 as the primary receptor and mediates regulatory effects on cell migration, proliferation, and angiogenesis considered major physiological and pathological features in health and disease.

Semaphorin-3E Produced by Immature Dendritic Cells Regulates Activated Natural Killer Cells Migration.

Natural killer (NK) cells and dendritic cells (DCs) are two innate immune cells that are critical in regulating innate and adaptive immunity. Cellular functions and migratory responses of NK or DC can be further regulated in NK-DC crosstalk that involves multiple cytokine signals and/or direct cell-cell contacts. Semaphorin-3E (Sema-3E) is a member of a large family of Semaphorin proteins that play diverse regulatory functions in different biological systems upon its binding to the cognate receptors.

Neuregulin-1 elicits a regulatory immune response following traumatic spinal cord injury.

Background: Spinal cord injury (SCI) triggers a robust neuroinflammatory response that governs secondary injury mechanisms with both degenerative and pro-regenerative effects. Identifying new immunomodulatory therapies to promote the supportive aspect of immune response is critically needed for the treatment of SCI. We previously demonstrated that SCI results in acute and permanent depletion of the neuronally derived Neuregulin-1 (Nrg-1) in the spinal cord.