1. T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis
- Author
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Francesca Barbieri, Maria Grazia Grasso, Serena Ruggieri, Roberto Furlan, Diego Centonze, Elisabetta Volpe, Claudio Gasperini, Silvia Rossi, Giovanna Borsellino, Gabriella Ruocco, Giulia Macchiarulo, Marco De Bardi, Caterina Motta, Luca Battistini, and Annamaria Finardi
- Subjects
Male ,Time Factors ,Myeloid ,Helper-Inducer ,T-Lymphocytes ,Cell Communication ,Relapsing-Remitting ,Dendritic cells ,Severity of Illness Index ,Disability Evaluation ,Interferon ,STAT5 Transcription Factor ,Phosphorylation ,Tomography ,Cells, Cultured ,Cultured ,biology ,Medicine (all) ,Interleukin-17 ,Imidazoles ,Interleukin ,hemic and immune systems ,T-Lymphocytes, Helper-Inducer ,General Medicine ,Middle Aged ,Magnetic Resonance Imaging ,Cerebrospinal fluid ,Phenotype ,STAT1 Transcription Factor ,medicine.anatomical_structure ,Interleukin-9 ,Multiple sclerosis ,T helper cells ,Adult ,Case-Control Studies ,Dendritic Cells ,Disease Progression ,Female ,Humans ,Inflammation Mediators ,Interferon Regulatory Factors ,Multiple Sclerosis, Relapsing-Remitting ,Signal Transduction ,Tomography, Optical Coherence ,Interleukin 12 ,Settore MED/26 - Neurologia ,Interleukin 17 ,medicine.drug ,Multiple Sclerosis ,Cells ,medicine ,Interleukin 9 ,Interleukin 3 ,CD40 ,Optical Coherence ,Immunology ,biology.protein - Abstract
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by persistent inflammation orchestrated by cluster of differentiation (CD) 4 T helper (Th) cells. In particular, Th1 and Th17 cells amplify, whereas T regulatory (Treg) cells moderate inflammation. The role of other Th subsets in MS is not clear. In the present study, we investigated the generation of different Th responses by human dendritic cells (DCs) in MS. We compared the production of several Th cytokines by naive CD4+ T-cells polarized with myeloid and plasmacytoid DCs (mDCs and pDCs) in healthy donors (HD) and relapsing–remitting (RR)-MS patients. We found that resiquimod-stimulated mDCs were able to activate Th17 differentiation, whereas pDCs induced interleukin (IL)-10-producing Th cells. Surprisingly, resiquimod-stimulated pDCs from MS patients also significantly induced the differentiation of Th9 cells, which produce IL-9 and are known to be involved in allergic diseases. We investigated the potential role of IL-9 in MS. We found that IL-9 activated signal transducer and activator of transcription (STAT) 1 and STAT5 phosphorylation and interfered with IL-17 and interferon (IFN) regulatory transcription factor (IRF)-4 expression in Th17-polarized cells. Moreover, in the cerebrospinal fluid (CSF) of 107 RR-MS patients, IL-9 inversely correlated with indexes of inflammatory activity, neurodegeneration and disability progression of MS. High levels of IL-9 were associated with the absence of IL-17 in the CSF of RR-MS patients. Our results demonstrate a Th9-inducing potential of pDCs in MS, suggesting an immunoregulatory role leading to attenuation of the exaggerated Th17 inflammatory response.
- Published
- 2015
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