TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response

Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction

Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leukocytes into the CNS, only few studies describe chemokine expression in neurons. Nevertheless, the expression of neuronal chemokines and the corresponding chemokine receptors in CNS cells under physiological and pathological conditions indicates that neuronal chemokines contribute to CNS cell interaction. In this study, we review recent studies describing neuronal chemokine expression and discuss potential roles of neuronal chemokines in neuron–astrocyte, neuron–microglia, and neuron–neuron interaction

Interaction de la chimiokine SDF-1a/CXCL12 avec le système vasopressinergique

La chimiokine SDF-1a (CXCL12) et son récepteur CXCR4 co-localisent avec l hormone antidiurétique, l arginine vasopressine (AVP) dans l hypothalamus et la neurohypophyse. Au cours de nos études, nous avons établi que : 1) le SDF-1a et l AVP présentent une distribution cellulaire spécifique dans les neurones des noyaux magnocellulaires hypothalamiques et sont localisés dans les mêmes vésicules neurosécrétoires de la neurohypophyse ; 2) le SDF-1a, par l intermédiaire du CXCR4, module l activité électrique du système à AVP et la libération plasmatique d AVP; 3) l expression du couple SDF-1a/CXCR4 est régulée lors de changements dans l équilibre hydrique suite à une déshydratation ou chez des animaux Brattleboro ; animaux déficients en synthèse centrale d AVP. Les données originales obtenues au cours de ce travail ouvrent un axe de recherche novateur dans l implication des chimiokines dans la régulation hydrique et plus généralement dans la régulation des fonctions neuroendocriniennesThe chemokine SDF-1a (CXCL12) and its receptor CXCR4 are co-localized with the antidiuretic hormone arginine vasopressin (AVP) in the hypothalamus and in the posterior pituitary. During our studies we demonstrated that: 1) SDF-1a and AVP present a selective cellular distribution inside the neuronal cell and can be found in the same dense core vesicles in the nerve terminals in the posterior pituitary; 2) SDF-1a can modulate, through CXCR4, the electrical activity of AVP neurons and plasma AVP release; 3) the expression of SDF-1a/CXCR4 is regulated when the hydro-osmotic balance is disturbed as in case of dehydration or in Brattleboro rats ; an endogenous knock-out model for brain AVP deficiency. The original data obtained during this work open new avenues in the implication of chemokines in the water balance regulation and more generally in neuroendocrine functionsPARIS-BIUP (751062107) / SudocSudocFranceF

Chemokines and chemokine receptors: New actors in neuroendocrine regulations

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