Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relaps
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SHORT REPORT
JOURNAL OF NEUROINFLAMMATION
Open Access
Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse Ana Leda F Longhini1†, Felipe von Glehn1,2†, Carlos Otávio Brandão1, Rosemeire FO de Paula1, Fernando Pradella1, Adriel S Moraes1, Alessandro S Farias1, Elaine C Oliveira1,3, Juan G Quispe-Cabanillas1, Cassiana Horta Abreu1,2, Alfredo Damasceno2, Benito P Damasceno2, Konstantin E Balashov4, Leonilda MB Santos1*
Abstract The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process. Introduction The pathogenesis of multiple sclerosis (MS) is mainly driven by central nervous system-invading encephalitogenic CD4 T lymphocytes of both the Th1 and Th17 types. These effector cells can be downregulated by regulatory T lymphocytes [1]. One subset of dendritic cells, the plasmacytoid dendritic cells (pDCs), has been given particular emphasis due to its importance in stimulating or down regulating effectors T cells in MS [2]. These pDCs are present in the cerebrospinal fluid (CSF), leptomeninges and demyelinating lesions of patients with MS [3]. These cells express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs secrete large amounts of type I interferon [4]. The use of type I interferon as an immunomodulator in the treatment of MS patients has proved beneficial for patients with the relapsing/ remitting form of MS (RRMS), and the production of * Correspondence: [email protected] † Contributed equally 1 Neuroimmunology Unit, Dept Genetics, Evolution and Bioagents, Biology Institute University of Campinas - UNICAMP Full list of author information is available at the end of the article
this cytokine by the pDCs may suggest an important immunomodulatory function of these cells. In the present study, the concentration of pDCs in the CSF and peripheral blood of MS patients during relapsing and remitting phases of the disease was determined and compared to what is present in other noninflammatory neurological diseases (OND).
Patients and Methods Peripheral venous blood (5 ml) and CSF (5-10 ml) samples were collected
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