{"id":23469,"date":"2020-12-11T13:07:45","date_gmt":"2020-12-11T11:07:45","guid":{"rendered":"https:\/\/irb.usi.ch\/?p=23469"},"modified":"2021-01-25T12:43:19","modified_gmt":"2021-01-25T10:43:19","slug":"gene-expression-to-vitamin-d-and-ifn-%ce%b2-new-paper-monticelli-lab","status":"publish","type":"post","link":"https:\/\/irb.usi.ch\/it\/news\/gene-expression-to-vitamin-d-and-ifn-%ce%b2-new-paper-monticelli-lab\/","title":{"rendered":"Modulation of gene expression in response to vitamin D and IFN-\u03b2: new paper by the Monticelli lab"},"content":{"rendered":"\t\t
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A recent publication in Frontiers in Immunology<\/em> by PhD student Niccol\u00f2 Bianchi and colleagues analyzed the changes in gene expression of lymphocytes treated with immunomodulatory factors.<\/p>

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by the presence of autoreactive leukocytes\u00a0infiltrating the central nervous system, potentially leading to inflammation and tissue damage. Autoreactive T cells play a crucial role in the pathophysiology of MS, in particular for their ability to produce inflammatory cytokines, such as GM-CSF and IL-17. An immunomodulatory treatment commonly used in therapy is IFN-\u03b2, which can counteract cytokine dysregulation in T cells, limiting GM-CSF production and increasing production of IL-10, an anti-inflammatory molecule. Epidemiological and clinical data also show that vitamin D deficiency correlates with an increased risk of MS and disease progression, pointing toward a beneficial role for this molecule in lowering MS activity and dampening inflammatory responses. Despite these clinical evidences, the mechanisms of action of vitamin D and IFN-\u03b2 in modulating T cell ability to produce cytokines remain elusive.<\/p>

In this study, the team of researchers from the Institute for Research in Biomedicine (Universit\u00e0 della Svizzera italiana), in collaboration with the Neurocenter of the Lugano Civico Hospital (EOC) sought to investigate the changes in expression of immune related genes and microRNA (miRNAs) in human T lymphocytes treated with IFN-\u03b2 and vitamin D, alone or in combination, to dissect the impact of these treatments on cytokine production and cell proliferation.<\/p>

The team found that the treatments acted primarily on memory T cell plasticity rather than promoting differentiation to a specific subset, leading to stable reduction of GM-CSF production. Furthermore, the treatments induced higher levels of IL-10, which however required concomitant engagement of the T cell receptor.<\/p>

In particular, while IFN-\u03b2 significantly induced the expression of IL-10<\/em> and other anti-inflammatory factors, it also upregulated IL-17<\/em> transcription. Vitamin D instead revealed a more complex role globally affecting T cell transcriptional program, inducing the expression of transcription factors such as RUNX1<\/em> (Figure 1).<\/em> The researchers also showed that T lymphocytes from MS patients responded to both treatments, confirming that IFN-\u03b2 and vitamin D modulated cytokine expression also during disease. Both treatments also impacted on the expression of miRNAs, post-transcriptional regulators of gene expression. Pro-inflammatory miRNAs, such as miR-155, were down-regulated by both treatments, indicating a potential contribution of these factors in modulating T cell functions. Indeed, T cells proliferation was significantly affected by the combined treatment. Collectively, this study provides a broad description of the transcriptional changes occurring in human T cells in response to treatments commonly administered in MS.<\/p>

This study, published in Frontiers in Immunology<\/em>, was realized in collaboration with Dr. Chiara Zecca, Neurocenter of Southern Switzerland, and it was financially supported by the NCCR \u201cRNA and Disease\u201d, the Swiss MS Society, the Swiss National Science Foundation and the Ceresio Foundation Lugano.<\/p>

Article:<\/strong><\/p>

Vitamin D and IFN-\u03b2 Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes<\/a><\/p>

Bianchi, N. Emming, S. Zecca, C. Monticelli, S.<\/p>

in Front Immunol (2020), DOI: 10.3389\/fimmu.2020.566781<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Vitamin D and IFN-<\/strong>\u03b2 modulate the phenotype of inflammatory T lymphocytes.<\/strong> Treatment of primary human T lymphocytes with the immunomodulatory factors vitamin D and IFN-\u03b2 leads to a phenotypic change to a state characterized by reduced inflammatory potential, as shown by reduced GM-CSF (encoded by the CSF2 <\/em>gene) and increased IL-10 expression. Such state is also associated with reduced proliferation, and altered expression of miRNAs, including miR-155 and miR-150.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

A recent publication in Frontiers in Immunology by PhD student Niccol\u00f2 Bianchi and colleagues analyzed the changes in gene expression of lymphocytes treated with immunomodulatory factors. Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by the presence of autoreactive leukocytes\u00a0infiltrating the central nervous system, potentially leading to inflammation and tissue damage. Autoreactive T cells […]<\/p>\n","protected":false},"author":4,"featured_media":23473,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[16],"tags":[],"yoast_head":"\nModulation of gene expression in response to vitamin D and IFN-\u03b2: new paper by the Monticelli lab - IRB USI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/irb.usi.ch\/it\/news\/gene-expression-to-vitamin-d-and-ifn-\u03b2-new-paper-monticelli-lab\/\" \/>\n<meta property=\"og:locale\" content=\"it_IT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Modulation of gene expression in response to vitamin D and IFN-\u03b2: new paper by the Monticelli lab - IRB USI\" \/>\n<meta property=\"og:description\" content=\"A recent publication in Frontiers in Immunology by PhD student Niccol\u00f2 Bianchi and colleagues analyzed the changes in gene expression of lymphocytes treated with immunomodulatory factors. Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by the presence of autoreactive leukocytes\u00a0infiltrating the central nervous system, potentially leading to inflammation and tissue damage. 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