Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation.

The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are.

Differing Outcome of Experimental Autoimmune Encephalitis in Macrophage/Neutrophil- and T Cell-Specific gp130-Deficient Mice.

gp130 cytokines are differentially involved in regulating the T helper (H) 17-driven pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis. Interleukin (IL)-6 directly promotes the development of TH17 cells through the gp130/IL-6R complex. By contrast, IL-27 has been shown to suppress a TH17 immune response by gp130/IL-27R-alpha (α) receptor ligation.

Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.

Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR).

Do not judge a cell by its cover--diversity of CNS resident, adjoining and infiltrating myeloid cells in inflammation.

Specialized populations of tissue-resident myeloid cells inhabit every organ of the body. While many of these populations appear similar morphologically and phenotypically, they exhibit great functional diversity. The central nervous system (CNS), as an immune privileged organ, possesses a unique tissue-resident macrophage population, the microglia, as well as numerous myeloid cell subsets at its boarders and barriers in CNS-adjoining tissues, namely the meninges, the perivascular space, and the choroid plexus.

Minimally invasive resection and vertebroplasty for an osteolytic C-1 metastasis of malignant meningioma: case report.

Malignant meningiomas are a rare but aggressive subset of intracranial meningiomas leading to a very limited life expectancy. The occurrence of spinal metastases in these tumors is an even rarer event. The described patient had an intracranial malignant meningioma and developed a symptomatic osteolytic contrast-enhancing lesion in the left C-1 lateral mass suspicious for metastasis.

USP18 lack in microglia causes destructive interferonopathy of the mouse brain.

Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called "microgliopathies". However, how the intracellular stimulation machinery in microglia is controlled is poorly understood.

In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE).

A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation.

Microglia are brain macrophages and, as such, key immune-competent cells that can respond to environmental changes. Understanding the mechanisms of microglia-specific responses during pathologies is hence vital for reducing disease burden. The definition of microglial functions has so far been hampered by the lack of genetic in vivo approaches that allow discrimination of microglia from closely related peripheral macrophage populations in the body.

Co-registration of the distribution of wall shear stress and 140 complex plaques of the aorta.

Previous studies provide evidence that atherosclerosis develops in vascular regions exposed to low wall shear stress (WSS) and high oscillatory shear index (OSI). 4D flow MRI was analyzed in 70 stroke patients with complex plaques (≥4 mm thickness, ulcerated or superimposed thrombi) and in 12 young healthy volunteers. The segmental distribution of peak systolic WSSsystole and OSI was quantified in analysis planes positioned directly at the location of 140 complex plaques found in the 70 patients.

IκB-ζ deficiency leaves epithelial cells high and dry.

The pathogenic mechanisms driving Sjögren's syndrome (SS) are unclear. In this issue of Immunity, Okuma et al. (2013) demonstrate that tissue-specific dysfunction, namely deficiency of the transcriptional regulator IκB-ζ in epithelial cells, rather than hematopoietic cell pathology, is sufficient to elicit SS-like inflammation.

How type I interferons shape myeloid cell function in CNS autoimmunity.

The precise mechanisms underlying the effects of IFN-I in CNS autoimmunity remain poorly understood despite the long-standing use of these cytokines as first-line disease-modifying drugs in the treatment of RRMS, a chronic demyelinating CNS autoimmune disease. Systemic use of IFN-I results in pleiotropic immunomodulation linking the innate and adaptive immune responses. Recent research has demonstrated that in the setting of CNS autoimmunity, IFNs-I have multiple effects on myeloid cell subsets, such as circulating monocytes, granulocytes, DCs, and tissue macrophages, such as microglia.

3D MRI provides improved visualization and detection of aortic arch plaques compared to transesophageal echocardiography.

Purpose: To compare 3D magnetic resonance imaging (3D MRI) with transesophageal echocardiography (TEE) for the detection of complex aortic plaques (≥4 mm thick, ulcerated, or containing mobile thrombi).

Materials And Methods: In all, 99 consecutive patients with acute cryptogenic stroke and ≥3 mm thick aortic plaques in TEE were prospectively included. 3D MRI comprised T1-weighted bright blood MRI with complete aortic coverage (spatial resolution 1 mm(3) ).

Estimation of global aortic pulse wave velocity by flow-sensitive 4D MRI.

The aim of this study was to determine the value of flow-sensitive four-dimensional MRI for the assessment of pulse wave velocity as a measure of vessel compliance in the thoracic aorta. Findings in 12 young healthy volunteers were compared with those in 25 stroke patients with aortic atherosclerosis and an age-matched normal control group (n = 9). Results from pulse wave velocity calculations incorporated velocity data from the entire aorta and were compared to those of standard methods based on flow waveforms at only two specific anatomic landmarks.

Complex plaques in the proximal descending aorta: an underestimated embolic source of stroke.

Background And Purpose: To investigate the incidence of retrograde flow from complex plaques (> or =4-mm-thick, ulcerated, or superimposed thrombi) of the descending aorta (DAo) and its potential role in embolic stroke.

Methods: Ninety-four consecutive acute stroke patients with aortic plaques > or =3-mm-thick in transesophageal echocardiography were prospectively included. MRI was performed to localize complex plaques and to measure time-resolved 3-dimensional blood flow within the aorta.