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Highlights d ACKR3 function was analyzed in b-arrestinand phosphorylation-deficient conditions d Phosphorylation regulates ACKR3-mediated scavenging independently of b-arrestins d b-Arrestin signaling is dispensable for CXCL12 guidance of interneuron migration d Absence and excess of CXCL12 cause similar interneuron motility defects

Inflammation triggers secondary brain damage after stroke. The meninges and other CNS border compartments serve as invasion sites for leukocyte influx into the brain thus promoting tissue damage after stroke. However, the post-ischemic immune response of border compartments compared to brain parenchyma remains poorly characterized. Here, we deeply characterize tissue-resident leukocytes in meninges and brain parenchyma and discover that leukocytes respond differently to stroke depending on their site of residence. We thereby discover a unique phenotype of myeloid cells exclusive to the brain after stroke. These stroke-associated myeloid cells partially resemble neurodegenerative disease-associated microglia. They are mainly of resident microglial origin, partially conserved in humans and exhibit a lipid-phagocytosing phenotype. Blocking markers specific for these cells partially ameliorates stroke outcome thus providing a potential therapeutic target. The injury-response of myeloid cells in the CNS is thus compartmentalized, adjusted to the type of injury and may represent a therapeutic target.

Background: Metabolic syndrome has become one of the most important public health problems with a growing prevalence in both developed and developing countries. Obesity is a major risk factor for obstructive sleep apnea (OSA), which is associated with significant cardiorespiratory morbidity. Aims: The aims of this study were to find out the prevalence of OSA in patients with metabolic syndrome and to highlight the importance of assessment of OSA in these patients. Methods: This cross-sectional analytical study was conducted on 100 subjects aged 30–60 years, comprising 50 cases of metabolic syndrome and 50 controls without metabolic syndrome. Overnight polysomnography was done in all the subjects. Prevalence and severity of OSA were assessed and compared between the two groups. Results: Prevalence of OSA was significantly higher (66%) in patients with metabolic syndrome than in subjects without metabolic syndrome (12%). Out of 33 (66%) OSA patients with metabolic syndrome, 8 (16%) had mild OSA, 11 (22%) had moderate OSA, and 14 (28%) had severe OSA. Increasing severity of OSA was associated with higher mean levels of all the metabolic syndrome parameters except serum high density lipoprotein (HDL). Conclusions: OSA is highly prevalent in patients with metabolic syndrome. Also, the increasing severity of OSA is associated with poorer control of diabetes, hypertension, and dyslipidemia, which are all components of metabolic syndrome. Therefore, effective treatment of metabolic syndrome can prevent and control OSA in these patients. Similarly, reducing the severity of OSA (by early diagnosis and treatment) in patients with metabolic syndrome might help to optimize control of blood sugar, blood pressure, and serum lipids, thereby reducing the risk of cardiovascular disease. Therefore, the need for screening metabolic syndrome patients for OSA has been reinforced by this study.

Innate lymphoid cells (ILCs) have a function in homeostasis and immune responses, but their role in ischemic brain insult is unknown. Here, we report that ILCs are not resident within the brain parenchyma during steady-state conditions, but are attracted after ischemic stroke. Specifically, we identified NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that Cxcl12 expressed at the blood-brain barrier is essential for NK cells and NKp46+ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevented NK cells from entering the infarct area. The lack of NK cell migration resulted in a higher neurological deficit in the beam-walk sensorimotor test. Our data show a new role for blood-brain barrier-derived Cxcl12 in attracting protective NK cells to ischemic brain lesions and identifies a new Cxcl12/ Cxcr4-mediated component of the innate immune response to stroke.