0000000000347338
AUTHOR
Maja Kitic
Novel Microglia Depletion Systems: A Genetic Approach Utilizing Conditional Diphtheria Toxin Receptor Expression and a Pharmacological Model Based on the Blocking of Macrophage Colony-Stimulating Factor 1 Receptor
Microglia are the main population of macrophage residing in the central nervous system (CNS). Depletion experiments gave important insights into the physiology and function of microglia in healthy and diseased CNS. Ablation of microglia can be achieved by application of pharmacological or genetic tools. Here, we describe two approaches to ablate microglia: an efficient genetic model that utilizes DTRMG mouse line that has diphtheria toxin receptor (DTR) expression regulated by the promoter activity of the fractalkine receptor (CX3CR1) gene, and a pharmacological model that utilizes the blocking of macrophage colony-stimulating factor 1 receptor (CSF-1R) with a blocking antibody. Both the ad…
The role of NG2 and OPC in induction and development of CNS inflammation
encephalitis (EAE) mouse models (J Neurosci 31:669, 2011; Brain 136:1760, 2013). Further, it has been shown that in addition to infiltrating leukocytes, astrocytes and microglia also exhibit high expression of EMMPRIN in diseased brain. EMMPRIN has been reported to interact with monocarboxylate transporter-1 (MCT-1) in astrocytes; the lattermediates lactate transport to neurons. Given that perturbation in energymetabolism can have catastrophic effects on homeostasis of the brain, it is paramount to understand EMMPRIN expression in astrocytes in normal andMS brain.We have used human fetal astrocytes (HFA) and determined their EMMPRIN levels by flow cytometry and microscopy. We found that HFA…
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling
NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…