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Università della Svizzera italiana

Epigenetic and transcriptional control of mast cell responses

Monticelli, Silvia ; Leoni

In: F1000 research, 2017, vol. 6, p. 2064

Mast cells are tissue-resident, innate immune cells present in most tissues of the body and are important effector and immunomodulatory cells. Differentiated mast cells typically are characterized by the surface expression of the receptors KIT and FcεRI, the latter especially being important for stimulation through IgE antibodies, although these cells have the ability to respond to a wide...

Università della Svizzera italiana

TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities

Montagner, Sara ; Leoni, Cristina ; Emming, Stefan ; Della Chiara, Giulia ; Balestrieri, Chiara ; Barozzi, Iros ; Piccolo, Viviana ; Togher, Susan ; Ko, Myunggon ; Rao, Anjana ; Natoli, Gioacchino ; Monticelli, Silvia

In: Cell reports, 2016, vol. 15, no. 7, p. 1566-1579

Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC). Here, we identified TET2 as a crucial regulator of mast cell differentiation and proliferation. In the absence of TET2, mast cells showed disrupted gene expression and altered genome-wide 5hmC deposition, especially at enhancers and in the proximity of...

Università della Svizzera italiana

Epigenetics of T lymphocytes in health and disease

Leoni, Cristina ; Vincenzetti, Lucia ; Emming, Stefan ; Monticelli, Silvia

In: Swiss Medical weekly, 2015, vol. 145, p. w14191

The risk of developing autoimmune diseases depends on both genetic and environmental factors, with epigenetic mechanisms of regulation potentially translating environmental cues into stable modifications in gene expression. Such stable memory of a functional state has been deciphered into a number of molecular mechanisms that collectively define the epigenetic status of a cell. In recent years,...

Università della Svizzera italiana

ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells

Mele, Federico ; Basso, Camilla ; Leoni, Cristina ; Aschenbrenner, Dominik ; Becattini, Simone ; Latorre, Daniela ; Lanzavecchia, Antonio ; Sallusto, Federica ; Monticelli, Silvia

In: Nature communications, 2015, vol. 6, p. 6431

T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset. In human memory TH17 cells, miR-181a...

Università della Svizzera italiana

MicroRNAs in hematopoietic development

Montagner, Sara ; Dehó, Lorenzo ; Monticelli, Silvia

In: BMC immunology, 2014, vol. 15, p. 14

Background: MicroRNAs (miRNAs) are short non-coding RNAs involved in the posttranscriptional regulation of a wide range of biological processes. By binding to complementary sequences on target messenger RNAs, they trigger translational repression and degradation of the target, eventually resulting in reduced protein output. MiRNA-dependent regulation of protein translation is a very widespread...

Università della Svizzera italiana

MiR-146a in immunity and disease

Rusca, Nicole ; Monticelli, Silvia

In: Molecular biology international, 2011, vol. 2011, p. 1-7

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of...

Università della Svizzera italiana

MiR-221 influences effector functions and actin cytoskeleton in mast cells

Mayoral, Ramon J. ; Deho, Lorenzo ; Rusca, Nicole ; Bartonicek, Nenad ; Saini, Harpreet Kaur ; Enright, Anton J. ; Monticelli, Silvia

In: Plos one, 2011, vol. 6, no. 10, p. e26133

Mast cells have essential effector and immunoregulatory functions in IgE-associated allergic disorders and certain innate and adaptive immune responses, but the role of miRNAs in regulating mast cell functions is almost completely unexplored. To examine the role of the activation-induced miRNA miR-221 in mouse mast cells, we developed robust lentiviral systems for miRNA overexpression and...

Università della Svizzera italiana

miR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation

Rusca, Nicole ; Dehò, Lorenzo ; Montagner, Sara ; Zielinski, Christina E. ; Sica, Antonio ; Sallusto, Federica ; Monticelli, Silvia

In: Molecular and cellular biology, 2012, vol. 32, no. 21, p. 4432-4444

The transcription factor NF-κB regulates the expression of a broad number of genes central to immune and inflammatory responses. We identified a new molecular network that comprises specifically the NF-κB family member NF-κB1 (p50) and miR-146a, and we show that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell...

Università della Svizzera italiana

Dnmt3a restrains mast cell inflammatory responses

Leoni, Cristina ; Montagner, Sara ; Rinaldi, Andrea ; Bertoni, Francesco ; Polletti, Sara ; Balestrieri, Chiara ; Monticelli, Silvia

In: Proceedings of the national academy of sciences, 2017, vol. 114, no. 8, p. E1490-E1499

DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in DNMT3A correlate with mast cell proliferative disorders in humans, the role of DNA methylation in mast cell biology is not understood. By using...

Accès public à partir du 30 janv. 2020
Università della Svizzera italiana

The contribution of active and passive mechanisms of 5mC and 5hmC removal in human T lymphocytes is differentiation- and activation-dependent

Vincenzetti, Lucia ; Leoni, Cristina ; Chirichella, Michele ; Kwee, Ivo ; Monticelli, Silvia

In: European Journal of Immunology, 2019, p. 1-15

In mammals, the 5’-methylcytosine (5mC) modification in the genomic DNA contributes to the dynamic control of gene expression. 5mC erasure is required for the activation of developmental programs and occurs either by passive dilution through DNA replication, or by enzymatic oxidation of the methyl mark to 5-hydroxymethylcytosine (5hmC), which can persist as such or undergo further oxidation...