Publications by authors named "William Barclay"

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including T17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in treating autoimmunity, there are currently no therapeutic interventions that specifically block encephalitogenic T17 cell migration. Here, we report integrin α3 as a T17 cell-selective determinant of pathogenicity in experimental autoimmune encephalomyelitis.

View Article and Find Full Text PDF

Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-negative (DN) 2 cells and after successful rearrangement and selection for functional TCRβ chains in DN3 thymocytes, which promotes the transition of DN4 cells to the DP stage. The signals driving the expansion of DN2 thymocytes are well studied.

View Article and Find Full Text PDF

Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically relevant orthopedic mouse model to study the impact of a common surgical procedure on the vulnerable brain. The mechanism underlying PNDs remains unknown.

View Article and Find Full Text PDF

Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory responses through their effector cytokines, IL-1β and IL-18. Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune conditions influenced by inflammasomes.

View Article and Find Full Text PDF

Pathologic roles of innate immunity in neurologic disorders are well described, but their beneficial aspects are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. Here, we report that Dectin-1 limited experimental autoimmune encephalomyelitis (EAE), while its downstream signaling molecule, Card9, promoted the disease.

View Article and Find Full Text PDF

-associated immune reconstitution inflammatory syndrome (C-IRIS) is identified upon immune reconstitution in immunocompromised patients, who have previously contracted an infection of (). C-IRIS can be lethal but how the immune system triggers life-threatening outcomes in patients is still poorly understood. Here, we establish a mouse model for C-IRIS with serotype A strain H99, which is highly virulent and the most intensively studied.

View Article and Find Full Text PDF

Pattern recognition receptors (PRRs) coordinate the innate immune response and have a significant role in the development of multiple sclerosis (MS). Accumulating evidence has identified both pathogenic and protective functions of PRR signaling in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Additionally, evidence for PRR signaling in non-immune cells and PRR responses to host-derived endogenous ligands has also revealed new pathways controlling the development of CNS autoimmunity.

View Article and Find Full Text PDF

Purpose Of Review: Despite the increasing number of clinical reports on immune reconstitution inflammatory syndrome (IRIS), mechanistic understanding of IRIS is still largely limited. The main focus of this review is to summarize animal studies, which were performed to better understand the cellular and molecular mechanisms underlying the pathology of IRIS.

Recent Findings: Three IRIS animal models have been reported.

View Article and Find Full Text PDF

Researchers have previously hypothesized autoimmune origins for narcolepsy on the basis of its strong genetic association with an MHC class II allele. In a recent issue of Nature, Latorre et al. (2018) discovered that narcolepsy patients had autoreactive T cells specific to the neuronal antigen hypocretin, providing more evidence of the potential immune origin of the disease.

View Article and Find Full Text PDF

The aptly named inflammasomes are powerful signaling complexes that sense inflammatory signals under a myriad of conditions, including those from infections and endogenous sources. The inflammasomes promote inflammation by maturation and release of the pro-inflammatory cytokines, IL-1β and IL-18. Several inflammasomes have been identified so far, but this review focuses mainly on the NLRP3 inflammasome.

View Article and Find Full Text PDF

The AP-1 factor basic leucine zipper transcription factor, ATF-like (BATF) is important for CD4 Th17, Th9, and follicular Th cell development. However, its precise role in Th2 differentiation and function remains unclear, and the requirement for BATF in nonallergic settings of type-2 immunity has not been explored. In this article, we show that, in response to parasitic helminths, Batf mice are unable to generate follicular Th and Th2 cells.

View Article and Find Full Text PDF