Publications by authors named "Y C Khaw"

21 Publications

Astrocytes lure CXCR2-expressing CD4 T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis.

Proc Natl Acad Sci U S A 2021 02;118(8)

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802;

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system driven by peripheral immune cell infiltration and glial activation. The pathological hallmark of MS is demyelination, and mounting evidence suggests neuronal damage in gray matter is a major contributor to disease irreversibility. While T cells are found in both gray and white matter of MS tissue, they are typically confined to the white matter of the most commonly used mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here, we used a modified EAE mouse model (Type-B EAE) that displays severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage. We show that CD4 T cells migrate to the spinal cord gray matter, preferentially to ventral horns. Compared to CD4 T cells in white matter, gray matter-infiltrated CD4 T cells were mostly immobilized and interacted with neurons, which are behaviors associated with detrimental effects to normal neuronal function. T cell-specific deletion of CXCR2 significantly decreased CD4 T cell infiltration into gray matter in Type-B EAE mice. Further, astrocyte-targeted deletion of TAK1 inhibited production of CXCR2 ligands such as CXCL1 in gray matter, successfully prevented T cell migration into spinal cord gray matter, and averted neuronal damage and motor dysfunction in Type-B EAE mice. This study identifies astrocyte chemokine production as a requisite for the invasion of CD4T cell into the gray matter to induce neuronal damage.
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http://dx.doi.org/10.1073/pnas.2017213118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923593PMC
February 2021

Iliac Telangiectatic Osteosarcoma - A Rare Presentation and Diagnostic Pitfall: A Case Report.

Malays Orthop J 2020 Nov;14(3):198-201

Department of Orthopaedics, Universiti Sains Malaysia, Kubang Kerian, Malaysia.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma and can be easily misdiagnosed as aneurysmal bone cyst. We report an atypical case of iliac telangiectatic osteosarcoma in a young healthy female, who presents with painful slow growing expansile lytic septate lesion in the left hemipelvis, which is initially treated as aneurysmal bone cyst. The diagnosis of aneurysmal bone cyst is made after histopathological examination of core needle biopsy. Her condition became unstable and massive bleeding is noted at the lesion site after sclerosant injection. She undergoes emergency hemipelvectomy and eventually the biopsy turns up to be telangiectatic osteosarcoma. Our case highlights that core needle biopsy is not useful in making diagnosis for iliac telangiectatic carcinoma. Hence, an open biopsy should be carried out in our case. This case also emphasises on careful evaluation for malignancy which is mandatory because bleeding from pelvis after an unsuitable treatment can be grave, to the extent that major amputation hemipelvectomy is an option. Even though telangiectatic osteosarcoma has the same prognosis and treatment with conventional osteosarcoma, the outcome of delayed treatment for telangiectatic osteosarcoma is not good due to the dilemma in establishing an early correct diagnosis.
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http://dx.doi.org/10.5704/MOJ.2011.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751993PMC
November 2020

Early-life-trauma triggers interferon-β resistance and neurodegeneration in a multiple sclerosis model via downregulated β1-adrenergic signaling.

Nat Commun 2021 01 4;12(1):105. Epub 2021 Jan 4.

University of Illinois at Urbana-Champaign Department of Comparative Biosciences, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA.

Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-β resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with β1 adrenergic receptor antagonist. Conversely, β1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell β1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of β1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.
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http://dx.doi.org/10.1038/s41467-020-20302-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782805PMC
January 2021

Th1-Dependent -Associated Immune Reconstitution Inflammatory Syndrome Model With Brain Damage.

Front Immunol 2020 29;11:529219. Epub 2020 Sep 29.

Department of Immunology, Duke University School of Medicine, Durham, NC, United States.

-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. C-IRIS in mice is induced by the adoptive transfer of CD4 T cells in immunocompromised -deficient mice infected with a low inoculum of The mice with C-IRIS exhibit symptoms which mimic clinical presentations of C-IRIS. This C-IRIS model is Th1-dependent and shows host mortality. This model is characterized with minimal lung injury, but infiltration of Th1 cells in the brain. C-IRIS mice also exhibited brain swelling with resemblance to edema and upregulation of aquaporin-4, a critical protein that regulates water flux in the brain in a Th1-dependent fashion. Our C-IRIS model may be used to advance our understanding of the paradoxical inflammatory phenomenon of C-IRIS in the context of neuroinflammation.
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http://dx.doi.org/10.3389/fimmu.2020.529219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550401PMC
April 2021

Optimization of the Freezing-Thawing Method for Extracting Phycobiliproteins from sp.

Molecules 2020 Aug 26;25(17). Epub 2020 Aug 26.

Department of Aquaculture, Faculty of Agriculture, Universiti Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia.

The freezing-thawing method had been reported to be the best phycobiliprotein extraction technique. However, optimum parameters of this extraction method for sp. (one of the major phycobiliprotein sources) still remained unclear. Hence, this study aimed to optimize the freezing-thawing parameters of phycobiliprotein extraction in sp. (UPMC-A0087). The optimization of the freezing-thawing method was conducted using different solvents, biomass/solvent ratios, temperatures, time intervals and freezing-thawing cycles. The extracted phycobiliproteins were quantified using a spectrophotometric assay. Double distilled water (pH 7) with a 0.50% / biomass/solvent ratio was the most efficient solvent in extracting high concentrations and purity of phycobiliproteins from sp. In addition, the combination of freezing at -80 °C (2 h) and thawing at 25 °C (24 h) appeared to be the optimum temperature and extraction time to obtain the highest amount of phycobiliproteins. A minimum of one cycle of freezing and thawing was sufficient for extracting high concentrations of phycobiliproteins. The findings from this study could reduce the cost and labor needed for extracting high quality phycobiliproteins. It also allowed the harvesting of large amounts of valuable phycobiliproteins.
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http://dx.doi.org/10.3390/molecules25173894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503228PMC
August 2020
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