Publications by authors named "Todd Shawler"
Long-term IS in transplant patients has significant morbidity, poorer quality of life, and substantial economic costs. TOL, defined as graft acceptance without functional impairment in the absence of IS, has been achieved in some pediatric LT recipients. Using mass cytometry, peripheral blood immunotyping was performed to characterize differences between tolerant patients and patients who are stable on single-agent IS.
View Article and Find Full Text PDFSoluble CD23 plays a role in the positive regulation of an IgE response. Engagement of the β2 adrenergic receptor (β2AR) on a B cell is known to enhance the level of both soluble CD23 and IgE, although the mechanism by which this occurs is not completely understood. In this study, we report that, in comparison with a CD40 ligand/IL-4-primed murine B cell alone, β2AR engagement on a primed B cell increased gene expression of a disintegrin and metalloproteinase (ADAM)10, which is the primary sheddase of CD23, as well as protein expression of both CD23 and ADAM10, in a protein kinase A- and p38 MAPK-dependent manner, and promoted the localization of these proteins to exosomes as early as 2 d after priming, as determined by both Western blot and flow cytometry and confirmed by electron microscopy.
View Article and Find Full Text PDFAutonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immune suppression are not known.
View Article and Find Full Text PDFMacrophage migration inhibitory factor (MIF) is a multipotent cytokine that is associated with clinical worsening and relapses in multiple sclerosis (MS) patients. The mechanism through which MIF promotes MS progression remains undefined. In this study, we identify a critical role for MIF in regulating CNS effector mechanisms necessary for the development of inflammatory pathology in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE).
View Article and Find Full Text PDFCXCR3, expressed mainly on activated T and NK cells, is implicated in a host of immunological conditions and can contribute either to disease resolution or pathology. We report the generation and characterization of a novel CXCR3 internal ribosome entry site bicistronic enhanced GFP reporter (CIBER) mouse in which enhanced GFP expression correlates with surface levels of CXCR3. Using CIBER mice, we identified two distinct populations of innate CD8(+) T cells based on constitutive expression of CXCR3.
View Article and Find Full Text PDFMacrophages exert divergent effects in the injured CNS, causing either neurotoxicity or regeneration. The mechanisms regulating these divergent functions are not understood but can be attributed to the recruitment of distinct macrophage subsets and the activation of specific intracellular signaling pathways. Here, we show that impaired signaling via the chemokine receptor CX3CR1 promotes recovery after traumatic spinal cord injury (SCI) in mice.
View Article and Find Full Text PDFMultiple sclerosis (MS) is an inflammatory disease of the CNS mediated by CD4(+) T cells directed against myelin antigens. Experimental autoimmune encephalomyelitis (EAE) is induced by immunization with myelin antigens like myelin oligodendrocyte glycoprotein (MOG). We have explored the transfer of EAE using MOG(35-55)-specific TCR transgenic (2D2) T cells.
View Article and Find Full Text PDFArticle Synopsis
- Chronic inflammation is linked to various diseases, and managing this inflammation is crucial for controlling diseases like multiple sclerosis (MS).
- Estrogen, particularly estriol (E3), plays a significant role in modulating immune responses, influencing immune cells and reducing inflammation, especially during pregnancy.
- E3 enhances the function of dendritic cells (DCs) to create a protective immune environment, which could lead to new therapies for autoimmune and chronic inflammatory diseases.
Multiple sclerosis (MS) is a chronic, debilitating disease of the central nervous system (CNS) characterized by demyelination and axon loss. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) has been shown to be elevated in the cerebrospinal fluid of patients during relapses. The purpose of this study was to evaluate a new small-molecule inhibitor of MIF and its ability to reduce the severity of an animal model of MS, experimental autoimmune encephalomyelitis (EAE).
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- * Research using an animal model (EAE) indicates that pregnancy reduces the likelihood and severity of MS-like symptoms when immunization occurs during this time, whereas symptoms worsen if immunization happens postpartum.
- * The study found that pregnant mice had lower levels of inflammatory cytokines like TNF-alpha and IL-17 compared to non-pregnant mice, suggesting that pregnancy creates a protective immune environment rather than simply suppressing the immune response.
Article Synopsis
- * Researchers tracked MBP-specific T cells using a fluorescent dye and found that these T cells moved to lymphoid tissues and Peyer's patches (PP) after MBP feeding, showing signs of proliferation and activation.
- * The findings suggest that administering autoantigens like MBP orally boosts MCP-1 in the gut, initiates early T cell movement and activation, and leads to the deletion of autoreactive T
Article Synopsis
- Dendritic cells (DCs) are crucial for linking the innate and adaptive immune responses, particularly in stimulating naïve T cells and managing autoimmune diseases.
- The study explores the differences between murine and human fms-like tyrosine kinase 3 ligand (mFL and hFL) in expanding DC populations, revealing that mFL-generated DCs resemble normal resting DCs more than their hFL counterparts.
- Findings indicate that while mFL and hFL equally expand DCs in vivo, mFL-derived bone marrow DCs are less mature but can become immunogenic and worsen the symptoms of a model autoimmune disease called experimental autoimmune encephalomyelitis (EAE).
Article Synopsis
- The study investigates how oral administration of myelin proteins can prevent and treat experimental autoimmune encephalomyelitis (EAE) and the role of the thymus in this process.
- Euthymic (normal thymus) mice show protection from EAE when fed myelin basic protein (MBP), while thymectomized mice (those without a thymus) do not exhibit this protection and have increased Th1 responses.
- The findings indicate that the thymus is crucial for the induction of regulatory T cells, which are necessary for suppressing immune responses and preventing EAE, highlighting the importance of thymus functionality in oral tolerance mechanisms.
Article Synopsis
- - Macrophage migration inhibitory factor (MIF) is linked to inflammatory and autoimmune diseases, specifically its role in experimental autoimmune encephalomyelitis (EAE).
- - Research using MIF-/- mice (mice lacking MIF) showed they had a different disease progression than normal mice, showing acute symptoms but not advancing further.
- - MIF-/- mice had higher levels of corticosterone and lower levels of key inflammatory cytokines (TNF-alpha, IFN-gamma, IL-2, IL-6), suggesting that MIF is critical for EAE progression by influencing stress hormone responses and the body's inflammatory reaction.
Article Synopsis
- Mice can be protected from EAE when they consume myelin basic protein (MBP).
- Thymectomized mice, which have had their thymus removed, do not show oral tolerance to MBP.
- The thymus plays a dual role in oral tolerance by deleting autoreactive T cells and producing regulatory T cells.