Hedwich F. Kuipers
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View article: The Diversified Astrocyte Developmental Programs are Modulated by Primary Ciliary Signaling
The Diversified Astrocyte Developmental Programs are Modulated by Primary Ciliary Signaling Open
Astrocyte diversity is greatly influenced by local environmental modulation. Here, we report that the vast majority of brain astrocytes across the entire brain possess a singular primary cilium, a specialized signaling antenna localized to…
View article: Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue
Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue Open
View article: Ultrasound and neuroinflammation: immune modulation via the heat shock response
Ultrasound and neuroinflammation: immune modulation via the heat shock response Open
Current pharmacological therapeutic approaches targeting chronic inflammation exhibit transient efficacy, often with adverse effects, limiting their widespread use - especially in the context of neuroinflammation. Effective interventions r…
View article: Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes
Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes Open
View article: Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes
Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes Open
Pancreatic β-cell dysfunction and death are central to the pathogenesis of type 2 diabetes (T2D). We have identified a novel role for the inflammatory extracellular matrix polymer hyaluronan (HA) in this pathophysiology. Low levels of HA a…
View article: FOXP3<sup>+</sup>regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues
FOXP3<sup>+</sup>regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues Open
FOXP3 + regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resource in vivo . Here, we show that Treg use heparanase (…
View article: Cuprizone-induced Demyelination in Mouse Brain is not due to Depletion of Copper
Cuprizone-induced Demyelination in Mouse Brain is not due to Depletion of Copper Open
The demyelinating effects of CPZ are not due to Cu deficiency but are instead consistent with acute toxicity of a CPZ + Cu complex.
View article: Hematopoietic Stem Cell Requirement for Macrophage Regeneration Is Tissue Specific
Hematopoietic Stem Cell Requirement for Macrophage Regeneration Is Tissue Specific Open
Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone intense scrutiny, in which now most TRMΦ …
View article: She Doesn’t Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders
She Doesn’t Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders Open
Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a…
View article: Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific
Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific Open
Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone intense scrutiny where now most TRMΦ are …
View article: Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection
Hyaluronan synthesis inhibition impairs antigen presentation and delays transplantation rejection Open
View article: Weekly injection of IL-2 using an injectable hydrogel reduces autoimmune diabetes incidence in NOD mice
Weekly injection of IL-2 using an injectable hydrogel reduces autoimmune diabetes incidence in NOD mice Open
View article: Hyaluronan Synthesis Inhibition Impairs Antigen Presentation and Delays Transplantation Rejection
Hyaluronan Synthesis Inhibition Impairs Antigen Presentation and Delays Transplantation Rejection Open
A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find…
View article: Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes
Sustained Release of IL-2 Using an Injectable Hydrogel Prevents Autoimmune Diabetes Open
Interleukin 2 (IL-2) is a promising therapy for autoimmune type 1 diabetes (T1D), but the short half-life in vivo (less than 6 minutes) limits effective tissue exposure to IL-2. Tissue exposure is required for the tolerogenic effects of IL…
View article: The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity
The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity Open
The heparan sulfate mimetic PG545 (pixatimod) is under evaluation as an inhibitor of angiogenesis and metastasis including in human clinical trials. We have examined the effects of PG545 on lymphocyte phenotypes and function. We report tha…
View article: Natural Tr1-like cells do not confer long-term tolerogenic memory
Natural Tr1-like cells do not confer long-term tolerogenic memory Open
IL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotempo…
View article: Author Index
Author Index Open
View article: 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition
4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition Open
View article: Author response: Natural Tr1-like cells do not confer long-term tolerogenic memory
Author response: Natural Tr1-like cells do not confer long-term tolerogenic memory Open
View article: Hyaluronan in immune dysregulation and autoimmune diseases
Hyaluronan in immune dysregulation and autoimmune diseases Open
View article: Phosphorylation of αB-crystallin supports reactive astrogliosis in demyelination
Phosphorylation of αB-crystallin supports reactive astrogliosis in demyelination Open
Significance αB-crystallin (CRYAB) is a protein involved in the protection of cells from stress and cell death, and is very highly produced in brain lesions in multiple sclerosis (MS). Astrocytes are the main non-neuronal cell type in the …
View article: The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice
The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice Open
Summary Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other inflammatory disorders where HA has been impli…
View article: Hyaluronan synthesis is necessary for autoreactive T-cell trafficking, activation, and Th1 polarization
Hyaluronan synthesis is necessary for autoreactive T-cell trafficking, activation, and Th1 polarization Open
Significance 4-methylumbelliferone (4-MU) is an oral drug that inhibits synthesis of hyaluronan, an extracellular matrix polymer implicated in autoimmunity. In the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis…
View article: Inhibition of hyaluronan synthesis restores immune tolerance during autoimmune insulitis
Inhibition of hyaluronan synthesis restores immune tolerance during autoimmune insulitis Open
We recently reported that abundant deposits of the extracellular matrix polysaccharide hyaluronan (HA) are characteristic of autoimmune insulitis in patients with type 1 diabetes (T1D), but the relevance of these deposits to disease was un…
View article: 4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer
4-Methylumbelliferone Treatment and Hyaluronan Inhibition as a Therapeutic Strategy in Inflammation, Autoimmunity, and Cancer Open
Hyaluronan (HA) is a prominent component of the extracellular matrix at many sites of chronic inflammation, including type 1 diabetes (T1D), multiple sclerosis, and numerous malignancies. Recent publications have demonstrated that when HA …