Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells.

Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting γδ T (γδT17) cells and Th17 cells.

Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease.

The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown.

An Emerging Role for SNARE Proteins in Dendritic Cell Function.

Dendritic cells (DCs) provide an essential link between innate and adaptive immunity. At the site of infection, antigens recognized by DCs via pattern-recognition receptors, such as Toll-like receptors (TLRs), initiate a specific immune response. Depending on the nature of the antigen, DCs secrete distinct cytokines with which they orchestrate homeostasis and pathogen clearance.

A role for syntaxin 3 in the secretion of IL-6 from dendritic cells following activation of toll-like receptors.

The role of dendritic cells (DCs) in directing the immune response is due in part to their capacity to produce a range of cytokines. Importantly, DCs are a source of cytokines, which can promote T cell survival and T helper cell differentiation. While it has become evident that soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptors (SNAREs) are involved in membrane fusion and ultimately cytokine release, little is known about which members of this family facilitate the secretion of specific cytokines from DCs.

Soluble factors from colonic epithelial cells contribute to gut homeostasis by modulating macrophage phenotype.

Intestinal macrophages originate from inflammatory blood monocytes which migrate to the intestine, where they differentiate into anti-inflammatory macrophages through a number of transitional stages. These macrophages typically remain hypo-responsive to commensal bacteria and food Ags in the intestine, yet also retain the ability to react to invading pathogens. In this study we examined the role of epithelial cells in inducing this intestinal macrophage phenotype.

Conjugated linoleic acid suppresses dendritic cell activation and subsequent Th17 responses.

PUFAs (polyunsaturated fatty acids) can modify immune responses, so they may have potential therapeutic effects in inflammatory disorders. We previously demonstrated that the cis-9, trans-11 isomer of the PUFA conjugated linoleic acid (CLA) can modulate dendritic cell (DC) cytokine production. Since DCs play a central role in initiating inflammation by directing T helper (Th) cell differentiation, here we examined the effects of CLA on DC maturation and migration and the subsequent generation of Th cell responses.

Syntaxin-4 is essential for IgE secretion by plasma cells.

The humoral immune system provides a crucial first defense against the invasion of microbial pathogens via the secretion of antigen specific immunoglobulins (Ig). The secretion of Ig is carried out by terminally differentiated B-lymphocytes called plasma cells. Despite the key role of plasma cells in the immune response, the mechanisms by which they constitutively traffic large volumes of Ig out of the cell is poorly understood.