Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions

INSERM, U842, Lyon, France.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(10):e3321. DOI: 10.1371/journal.pone.0003321
Source: PubMed


In many neuroinflammatory diseases, dendritic cells (DCs) accumulate in several compartments of the central nervous system (CNS), including the cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought to play a major role in the initiation and perpetuation of CNS-targeted autoimmune responses. We previously reported that, in normal rats, DCs injected intra-CSF migrated outside the CNS and reached the B-cell zone of cervical lymph nodes. However, there is yet no information on the migratory behavior of CSF-circulating DCs under neuroinflammatory conditions.

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    • "However, some immune cells may infiltrate into the CSF, which is produced by choroid plexus epithelia and flows into the subarachnoid space. Importantly, the CSF drains into cervical lymph nodes, enabling peripheral immune cells to recognize and respond to CNS antigens in the absence or presence of inflammation (11, 12). Accordingly, the subarachnoid space and choroid plexus of healthy mice contain substantial numbers of T cells and are heavily populated by myeloid cells, including DCs (13). "
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    ABSTRACT: Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuroimmune communications mediated by dopamine. Studies of dendritic cells (DCs) revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs). Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4(+) T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS) and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis (RA). The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or RA. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.
    Full-text · Article · Mar 2014 · Frontiers in Immunology
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    • "DCs emigrating from the brain have been shown to infiltrate peripheral lymphatic organs, inducing a local immune response and directing antigen-specific T cells back to the brain [26]–[28]. Notably, in rodents and ruminants, the cerebrospinal fluid (CSF) flows into the CLNs [24], [29], which may be associated with immune surveillance of the CNS. In addition, myelin antigens presented by DCs have been detected in the CLNs of a primate model of an inflammatory demyelinating disorder [29]. "
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    ABSTRACT: Traumatic injury to the central nervous system (CNS) triggers a robust inflammatory response that leads to axonal damage and secondary degeneration of spared tissue. In contrast, some immune responses have neuroprotective effects. However, detailed information regarding the dynamics of immune responses after traumatic CNS injury is still unavailable. In the present study, changes in the immune cells present in the injured brain, spleen, and cervical lymph nodes (CLNs), which are draining lymphatic organs from the CNS, were analyzed after controlled cortical impact (CCI) by flow cytometry and immunohistochemistry. The number of neutrophils and macrophages that infiltrated the injured brain immediately increased 1 d post-injury and declined rapidly thereafter. In the injured brain, resident microglia showed a bimodal increase during the first week and in the chronic phase (≥3 weeks) after injury. Increase in the Iba-1(+) microglia/macrophages was observed around the injured site. Morphologic analysis showed that Iba-1(+) cells were round at 1 week, whereas those at 3 weeks were more ramified. Furthermore, CD86(+)/CD11b(+) M1-like microglia increased at 4 weeks after CCI, whereas CD206(+)/CD11b(+) M2-like microglia increased at 1 week. These results suggest that different subsets of microglia increased in the acute and chronic phases after CCI. Dendritic cells and T cells increased transiently within 1 week in the injured brain. In the CLNs and the spleen, T cells showed dynamic changes after CCI. In particular, the alteration in the number of T cells in the CLNs showed a similar pattern, with a 1-week delay, to that of microglia in the injured brain. The data from this study provide useful information on the dynamics of immune cells in CNS injuries.
    Full-text · Article · Jul 2012 · PLoS ONE
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    • "In fact during neuroinflammatory conditions, DCs accumulate in the CSF, as well as in perivascular spaces. These findings suggest that the CSF might be a major route for transporting DCs from the CNS to the lymphoid organs (Hatterer et al., 2008). Additionally, it has been reported that DCs injected into the CSF preferentially migrate to B cell follicles within the cervical LNs; suggesting that under neuro-inflammatory conditions, specific mechanisms direct the DCs migration to this location (Hatterer et al., 2006). "
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    ABSTRACT: Immune surveillance in the central nervous system (CNS) was considered impossible because: (i) the brain parenchyma is separated from the blood circulation by the blood-brain barrier (BBB); (ii) the brain lacks lymphatic drainage and (iii) the brain displays low major histocompatibility complex class II (MHCII) expression. In this context, the BBB prevents entry of immune molecules and effector cells to the CNS. The absence of lymphatic vessels avoids CNS antigens from reaching the lymph nodes for lymphocyte presentation and activation. Finally, the low MHCII expression hinders effective antigen presentation and re-activation of T cells for a competent immune response. All these factors limit the effectiveness of the afferent and efferent arms necessary to carry out immune surveillance. Nevertheless, recent evidence supports that CNS is monitored by the immune system through a modified surveillance circuit; this work reviews these findings.
    Full-text · Article · Jan 2012 · Brain Behavior and Immunity
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