CD4+ T cell microRNAs signatures in multiple sclerosis
Responsable du Stage : Frédérique MICHEL
Tél : 01 45 68 86 38 Fax : 01 40 61 32 04 E-mail: firstname.lastname@example.org
Résumé du Projet de Stage
We study the immunomodulatory activity of type I interferons (IFNa/b) on CD4+ T cell responses in patients with multiple sclerosis (MS) and healthy donors. This autoimmune and inflammatory disease is characterized by recurrent attacks of the central nervous system by infiltrated immune cells, leading to gradual axonal demyelination and neurodegeneration, physical and cognitive disabilities. The common form of the disease is relapsing-remitting and can be treated by IFNb as a first-line therapy. However, the disease can evolve in time towards a more severe secondary progressive form. In this context, we are interested in understanding the molecular mechanisms utilized by pathogenic CD4+ T cells and to identify cellular and molecular biomarkers associated with disease activity.
We have previously found microRNAs (miRNAs) whose level is modulated by IFNb in activated CD4+ T cells of healthy donors. MiRNAs are small non-coding RNAs that mainly bind to the 3’ untranslated region of messenger RNAs, causing their degradation and/or reduced translation. They post-transcriptionally regulate gene networks involved in a number of vital biological processes, in particular T cell differentiation and function. In addition, miRNA signatures have been reported to differ according to the immune cell type and physio-pathological context. The objectives of the project are: 1- to determine by RT-qPCR if a set of miRNAs is differentially expressed in CD4+ T cell subsets that have been and will be sorted by flow cytometry from blood samples of MS patients and healthy subjects. 2- to study the functional impact of some miRNAs in the T cell response using a CD4+ T cell line model and primary CD4+ T cells. 3- to investigate whether miRNAs signatures can be associated with disease activity.
– Devi-Marulkar P, Moraes-Cabe C, Campagne P, Corre B, Meghraoui-Kheddar A, Bondet V, Llibre A, Duffy D, Maillart E, Papeix C, Pellegrini S, Michel F. Altered Immune Phenotypes and HLA-DQB1 Gene Variation in Multiple Sclerosis Patients Failing Interferon β Treatment. Front Immunol. 2021 May 25;12:628375. doi: 10.3389/fimmu.2021.628375. eCollection 2021. PMID: 34113337
– Rubino E, Cruciani M, Tchitchek N, Le Tortorec A, Rolland AD, Veli Ö, Vallet L, Gaggi G, Michel F, Dejucq-Rainsford N, Pellegrini S. Human Ubiquitin-Specific Peptidase 18 Is Regulated by microRNAs via the 3’Untranslated Region, A Sequence Duplicated in Long Intergenic Non-coding RNA Genes Residing in chr22q11.21. Front Genet. 2021 Feb 3;11:627007. doi: 10.3389/fgene.2020.627007. PMID: 33633774
– Li Z, Rotival M, Patin E, Michel F, Pellegrini S. 2020. Two common disease-associated TYK2 variants impact exon splicing and TYK2 dosage. PLoS One. 2020 Jan 21;15(1):e0225289. doi: 10.1371/journal.pone.0225289. eCollection 2020. PMID: 31961910
– Azébi S, Batsché E, Michel F, Kornobis E, Muchardt C. 2019. Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells. EMBO J. 38(12):e101107. Epub 2019 May 8. PMID: 31068361 DOI: 10.15252/embj.2018101107
– U. Govender, B. Corre, Y. Bourdache, S. Pellegrini and F. Michel. 2017. Type I interferon-enhanced IL-10 expression in human CD4 T cells is regulated by STAT3, STAT2, and BATF transcription factors. J. Leukoc. Biol. 101(5):1181-1190. Epub 2017 Feb 27. PMID: 28242623 DOI :10.1189/jlb.2A0416-187R
Ce projet s’inscrit-il dans la perspective d’une thèse :
Intitulé de l’Unité : Signalisation des cytokines, Institut Pasteur, INSERM U1224
Nom du Responsable de l’Unité : Sandra Pellegrini
Nom du Responsable de l’Équipe : Frédérique MICHEL
Adresse : Institut Pasteur, Département d’Immunologie, 25 rue du Dr. Roux, 75015, Paris