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Start Over Author "Sambucci, Manolo" Topic cell differentiation
2 results on '"Sambucci, Manolo"'

1. The p38 mitogen-activated protein kinase cascade modulates T helper type 17 differentiation and functionality in multiple sclerosis.

Author

Di Mitri D, Sambucci M, Loiarro M, De Bardi M, Volpe E, Cencioni MT, Gasperini C, Centonze D, Sette C, Akbar AN, Borsellino G, and Battistini L

Subjects
Adenosine Triphosphatases metabolism, Adult, Case-Control Studies, Cation Transport Proteins metabolism, Cells, Cultured, Copper-Transporting ATPases, Enzyme Activation, Eukaryotic Initiation Factor-4E metabolism, Female, Humans, Interleukin-17 metabolism, Interleukins metabolism, Middle Aged, Multiple Sclerosis, Relapsing-Remitting immunology, Phenotype, Phosphorylation, Th17 Cells immunology, Cell Differentiation, Lymphocyte Activation, MAP Kinase Signaling System, Multiple Sclerosis, Relapsing-Remitting enzymology, Th17 Cells enzymology, p38 Mitogen-Activated Protein Kinases metabolism
Abstract

The p38 mitogen-activated protein kinase cascade is required for the induction of a T helper type 17 (Th17) -mediated autoimmune response, which underlies the development and progression of several autoimmune diseases, such as experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis (MS). However, the contribution of p38 phosphorylation to human Th cell differentiation has not been clarified. Here we demonstrate that the p38 signalling pathway is implicated in the generation of Th17 lymphocytes from human CD4(+)  CD27(+)  CD45RA(+) naive T cells, both in healthy donors and in patients affected by the relapsing-remitting form of MS. Our data also indicate that p38 activation is essential for interleukin-17 release from central memory lymphocytes and committed Th17 cell clones. Furthermore, CD4(+) T cells isolated from individuals with relapsing-remitting MS display an altered responsiveness of the p38 cascade, resulting in increased p38 phosphorylation upon stimulation. These findings suggest that the p38 signalling pathway, by modulating the Th17 differentiation and response, is involved in the pathogenesis of MS, and open new perspectives for the use of p38 inhibitors in the treatment of Th17-mediated autoimmune diseases., (© 2015 John Wiley & Sons Ltd.)

Published
2015
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2. Increased Foxp3+ Regulatory T Cells in Poly(ADP-Ribose) Polymerase-1 Deficiency

Author

Manolo Sambucci, Maria Manuela Rosado, Claudio Pioli, Federica Laudisi, Francesca Nasta, Pioli, Claudio, Rosado, Maria Manuela, Sambucci, Manolo, Laudisi, Federica, and Nasta, Francesca

Subjects
Regulatory T cell differentiation, lymphocyte differentiation, Immunology, lymphocyte differentiation, regulatory T cells, PARP-1, Immunology, Poly (ADP-Ribose) Polymerase-1, PARP-1, Cell Separation, Thymus Gland, T-Lymphocytes, Regulatory, regulatory T cells, TCIRG1, Mice, Interleukin 21, T-Lymphocyte Subsets, Animals, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Mice, Knockout, CD40, biology, Reverse Transcriptase Polymerase Chain Reaction, ZAP70, FOXP3, Cell Differentiation, Forkhead Transcription Factors, Flow Cytometry, Cell biology, Mice, Inbred C57BL, biology.protein, Lymph Nodes, Poly(ADP-ribose) Polymerases, Spleen
Abstract

Growing evidence is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. In the current study, we investigated the effects of PARP-1 deficiency on regulatory T cell differentiation. Increased numbers of regulatory CD4+CD25+/Foxp3+ T cells were found in thymus, spleen, and lymph nodes of PARP-1 knockout (KO) mice compared with wild-type (WT) controls. The increased frequency of regulatory T cells in the periphery resulted in impaired CD4 cell proliferation and IL-2 production, which could be restored by CD25+ cell depletion. Phenotype and inhibitory functions of PARP-1 KO regulatory T cells were similar to WT cells, indicating that PARP-1 affects regulatory T cell differentiation rather than function. Purified naive CD4 cells from PARP-1 KO mice stimulated in vitro expressed forkhead box p3 mRNA at higher levels and generated a greater number of Foxp3+ cells (inducible regulatory T [iTreg] cells) than the WT counterpart. This finding was due to a higher rate of naive CD4 cell to Foxp3+ iTreg cell conversion rather than to higher resistance to apoptosis induction. Interestingly, PARP-1 deficiency did not affect retinoid-related orphan receptor-γt mRNA expression and differentiation of purified naive CD4 cells to Th17 cells. PARP-1 KO iTreg cells showed features similar to WT regulatory T cells, suggesting that modulation of PARP-1 during the immune response might be used to induce greater numbers of functional regulatory T cells. In conclusion, our findings represent the first evidence that PARP-1 can affect regulatory T cell differentiation and open new perspectives on potential targets for modulating immune responses.

Published
2010

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