IL-20 Cytokines Are Involved in the Repair of Airway Epithelial Barrier: Implication in Exposure to Cigarette Smoke and in COPD Pathology.

Background: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking COPD to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding.

T Lymphocyte Serotonin 5-HT Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients.

Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far.

Safe and Efficient Sigma1 Ligand: A Potential Drug Candidate for Multiple Sclerosis.

Multiple Sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS). Current management strategies suppress or modulate immune function, all with consequences and known side effects. They demonstrate a high level of success in limiting new relapses.

Serodolin, a β-arrestin-biased ligand of 5-HT receptor, attenuates pain-related behaviors.

G protein–coupled receptors (GPCRs) are involved in regulation of manifold physiological processes through coupling to heterotrimeric G proteins upon ligand stimulation. Classical therapeutically active drugs simultaneously initiate several downstream signaling pathways, whereas biased ligands, which stabilize subsets of receptor conformations, elicit more selective signaling. This concept of functional selectivity of a ligand has emerged as an interesting property for the development of new therapeutic molecules.

Production of Interleukin-20 cytokines limits bacterial clearance and lung inflammation during infection by Streptococcus pneumoniae.

Background: Streptococcus pneumoniae is the leading cause of bacterial pneumonia worldwide. Previous reports showed that IL-20 cytokines (IL-19, IL-20 and IL-24) are induced and have an immuno-regulatory function during cutaneous infection. In the current study, our aim was to demonstrate the implication of IL-20 cytokines and their receptors and their role during experimental pneumococcal infection.

Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice.

T helper (Th)17 immune response participates in allergic lung inflammation and asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL-17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia, cytokine and chemokine production as found in absence of IL-17RA.

Physical interaction between neurofibromin and serotonin 5-HT6 receptor promotes receptor constitutive activity.

Active G protein-coupled receptor (GPCR) conformations not only are promoted by agonists but also occur in their absence, leading to constitutive activity. Association of GPCRs with intracellular protein partners might be one of the mechanisms underlying GPCR constitutive activity. Here, we show that serotonin 5 hydroxytryptamine 6 (5-HT) receptor constitutively activates the Gs/adenylyl cyclase pathway in various cell types, including neurons.

Protein kinase Cθ controls type 2 innate lymphoid cell and T2 responses to house dust mite allergen.

Background: Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in T2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble T2 cells and produce the T2 cytokines IL-5 and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct T2 responses in patients with allergic lung inflammation remains unknown.

Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation.

The cysteine protease caspase-1 (Casp-1) contributes to innate immunity through the assembly of NLRP3, NLRC4, AIM2, and NLRP6 inflammasomes. Here we ask whether caspase-1 activation plays a regulatory role in house dust mite (HDM)-induced experimental allergic airway inflammation. We report enhanced airway inflammation in caspase-1-deficient mice exposed to HDM with a marked eosinophil recruitment, increased expression of IL-4, IL-5, IL-13, as well as full-length and bioactive IL-33.

Thymic Stromal Lymphopoietin Enhances Th2/Th22 and Reduces IL-17A in Protease-Allergen-Induced Airways Inflammation.

Background. Thymic stromal lymphopoietin (TSLP) is induced in allergic skin and lung inflammation in man and mice. Methods.