Arf6 regulates energy metabolism in neutrophils.

The small GTPase Arf6 regulates many cellular processes, including cytoskeletal remodeling, receptor endocytosis, and pathogen phagocytosis. Arf6 silencing in neutrophil (PMN)-like cells is well-known to inhibit chemotactic peptide-mediated activation of phospholipase D, the oxidative burst, and β2 integrin-dependent adhesion. In conditional knockout (cKO) mice, the migration to inflammatory sites of Arf6-deficient PMNs was diminished and associated with reduced cell surface expression of β2 integrins.

Expression of the myeloid inhibitory receptor CLEC12A correlates with disease activity and cytokines in early rheumatoid arthritis.

The myeloid inhibitory receptor CLEC12A negatively regulates inflammation. Reduced CLEC12A expression enhances inflammation in CLEC12A knock-out mice with collagen antibody-induced arthritis. Moreover, CLEC12A internalisation augments human neutrophil activation.

Deletion of and Enhances Skin Hyperplasia and Promotes the Th17 Response in Imiquimod-Induced Psoriasis.

High concentrations of the damage-associated molecular patterns S100A8 and S100A9 are found in skin and serum from patients suffering from psoriasis, an IL-17-related disease. Notably, although the expression of these proteins correlates with psoriatic disease severity, the exact function of S100A8 and S100A9 in psoriasis pathogenesis remains unclear. In this study, we investigated the role of S100A8 and S100A9 in psoriasis-associated skin hyperplasia and immune responses using and mice in an imiquimod-induced model of psoriasis.

Enhanced myelopoiesis and aggravated arthritis in S100a8-deficient mice.

Expressed strongly by myeloid cells, damage-associated molecular pattern (DAMP) proteins S100A8 and S100A9 are found in the serum of patients with infectious and autoimmune diseases. Compared to S100A9, the role of S100A8 is controversial. We investigated its biological activity in collagen-induced arthritis using the first known viable and fertile S100a8-deficient (S100a8-/-) mouse.

The use of leukocytes' secretome to individually target biological therapy in autoimmune arthritis: a case report.

Background: Biological agents have allowed remarkable improvement in controlling autoimmune arthropathies, although none of the numerous biologics readily available represent a universal treatment standard. Moreover, classical and genetic predictors are currently unsatisfactory to predict individual response to a biologic, and the best treatment selection is still based on a trial-and-error approach. Here, we report a clinical case demonstrating the usefulness of examining the leukocytes' secretome of patients.

S100A8/A9 and sRAGE kinetic after polytrauma; an explorative observational study.

Background: Following tissue injury after trauma, the activation of innate immune pathways results in systemic inflammation, organ failure and an increased risk of infections. The objective of this study was to characterize the kinetics of the S100A8/S100A9 complex, a new-recognized alarmin, as well as its soluble receptor sRAGE, over time after trauma as potential early biomarkers of the risk of organ damage.

Methods: We collected comprehensive data from consenting patients admitted to an ICU following severe trauma.

Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway.

Effector T cell migration through the tissue extracellular matrix (ECM) is an important step of the adaptive immune response and in the development of inflammatory diseases. However, the mechanisms involved in this process are still poorly understood. In this study, we addressed the role of a collagen receptor, the discoidin domain receptor 1 (DDR1), in the migration of Th17 cells.

Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss.

Th17 cells are critical effectors in inflammation and tissue damage such as bone erosion, but the mechanisms regulating their activation in this process are not fully understood. In this study, we considered the cooperation between cytokine receptors and integrin pathways in Th17-osteoclast function. We found that human Th17 cells coexpress IL-7R and the collagen-binding integrin α2β1 (CD49b), and IL-7 increases their adhesion to collagen via α2β1 integrin.

Regulation of TLR3 Activation by S100A9.

Recognition of viral dsRNA by endosomal TLR3 activates innate immune response during virus infection. Trafficking of TLR3 to the endolysosomal compartment arising from fusion of late endosome (LE) with lysosome is required for recognition and detection of pathogen associated molecular patterns, which results in activation of the TLR3-dependent signaling cascade. Existing knowledge about the mechanism(s) and cellular factor(s) governing TLR3 trafficking is limited.

Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux.

S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway.

α2β1 integrin regulates Th17 cell activity and its neutralization decreases the severity of collagen-induced arthritis.

Th17 cells play a critical role in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms by which these cells regulate the development of RA are not fully understood. We have recently shown that α2β1 integrin, the receptor of type I collagen, is the major collagen-binding integrin expressed by human Th17 cells. In this study, we examined the role of α2β1 integrin in Th17-mediated destructive arthritis in the murine model of collagen-induced arthritis (CIA).

An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis.

Objective: The S100A9 and S100A8 proteins are highly expressed by neutrophils and monocytes and are part of a group of damage-associated molecular pattern molecules that trigger inflammatory responses. Sera and synovial fluids of patients with rheumatoid arthritis (RA) contain high concentrations of S100A8/A9 that correlate with disease activity.

Methods: In this study, we investigated the importance of S100A9 in RA by using neutralizing antibodies in a murine lipopolysaccharide-synchronized collagen-induced arthritis model.

Influence of cigarette smoke on the arginine pathway in asthmatic airways: increased expression of arginase I.

Background: Up to 30% of asthmatic subjects are smokers, and smoking might be an important contributor to asthma pathology. Inducible nitric oxide synthase (iNOS), ornithine decarboxylase (ODC), and arginase I are involved in the arginine pathway. We have shown that arginase I and iNOS are upregulated in asthma.

Interleukin-18 and gamma interferon production by oral epithelial cells in response to exposure to Candida albicans or lipopolysaccharide stimulation.

Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans. Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses.