Léa Flippe

ORCID: 0000-0002-8521-5267
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About
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Research Areas
  • Pluripotent Stem Cells Research
  • T-cell and B-cell Immunology
  • CRISPR and Genetic Engineering
  • CAR-T cell therapy research
  • Immune Cell Function and Interaction
  • Adrenal Hormones and Disorders
  • Immunotherapy and Immune Responses
  • Biomedical Ethics and Regulation
  • Renal and related cancers
  • Prenatal Screening and Diagnostics
  • Stress Responses and Cortisol
  • Dermatology and Skin Diseases
  • Chemokine receptors and signaling
  • Advanced Biosensing Techniques and Applications
  • Diabetes and associated disorders
  • Monoclonal and Polyclonal Antibodies Research
  • Multiple Sclerosis Research Studies
  • Immune Response and Inflammation
  • 3D Printing in Biomedical Research
  • Hormonal Regulation and Hypertension

Nantes Université
2018-2023

Inserm
2018-2023

Center for Research in Transplantation and Translational Immunology
2020-2023

Centre National de la Recherche Scientifique
2021-2022

Institut de Transplantation Urologie en Nephrologie
2018-2020

Centre d'Investigation Clinique de Nantes
2020

Centre Hospitalier Universitaire de Nantes
2020

Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access human embryos placentas is limited, thus preventing establishment of hTSCs diverse genetic backgrounds associated with placental disorders. Here, we show that can be generated numerous using post-natal via two alternative methods: (1) somatic cell reprogramming adult fibroblasts OCT4, SOX2, KLF4, MYC (OSKM) (2) fate...

10.1016/j.celrep.2020.108419 article EN cc-by-nc-nd Cell Reports 2020-11-01

Abstract Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of embryonic origin offer potential to generate patient-specific cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, iPSCs (hiPSCs), restricting their post-implantation development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we...

10.1038/s41467-017-02107-w article EN cc-by Nature Communications 2018-01-18

Abstract Over a decade after their discovery, induced pluripotent stem cells (iPSCs) have become major biological model. The iPSC technology allows generation of from somatic bearing any genomic background. challenge ahead us is to translate human iPSCs (hiPSCs) protocols into clinical treatment. To do so, we need improve the quality hiPSCs produced. In this study report reprogramming multiple patient urine-derived cell lines with mRNA reprogramming, which, date, one fastest and most...

10.1038/s41598-018-32645-2 article EN cc-by Scientific Reports 2018-09-19

Abstract Autoimmune regulator (AIRE) deficiency in humans induces a life-threatening generalized autoimmune disease called polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), and no curative treatments are available. Several models of AIRE-deficient mice have been generated, although they useful understanding the role AIRE central tolerance, do not reproduce accurately APECED symptoms, thus there is still need for an animal model displaying APECED-like disease. We assessed, this...

10.4049/jimmunol.1701318 article EN The Journal of Immunology 2018-06-29

Targeted monoclonal antibody (mAb) therapies show great promise for the treatment of transplant rejection and autoimmune diseases by inducing more specific immunomodulatory effects than broadly immunosuppressive drugs routinely used. We recently described therapeutic advantage targeting CD45RC, expressed at high levels conventional T (Tconv) cells (CD45RChi), their precursors, terminally differentiated (TEMRA) cells, but not regulatory (Tregs; CD45RClo/-). demonstrated efficacy anti-CD45RC...

10.1172/jci156507 article EN cc-by Journal of Clinical Investigation 2022-02-15

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. Studies immune dysfunction in MS have mostly focused on CD4+ Tregs, but role CD8+ Tregs remains largely unexplored. We previously evidenced suppressive properties rat human CD8+CD45RClow/neg from healthy individuals, expressing Forkhead box P3 (FOXP3) acting through interferon-gamma (IFN-γ), transforming growth factor beta (TGFβ), interleukin-34 (IL-34). secretions to regulate responses control diseases...

10.1212/nxi.0000000000200016 article EN cc-by-nc-nd Neurology Neuroimmunology & Neuroinflammation 2022-10-20

Cell therapy using T cells has revolutionized medical care in recent years but limitations are associated with the difficulty of genome editing cells, production a sufficient number and standardization product. Human pluripotent stem (hPSCs) can self-renew differentiate into to provide standardized homogenous product defined origin indefinite quantity, therefore they great potential alleviate therapeutic cell production. The differentiation hPSCs takes place two steps: first induction...

10.3389/fcell.2020.577464 article EN cc-by Frontiers in Cell and Developmental Biology 2020-10-20

Immunotherapy using primary T cells has revolutionized medical care in some pathologies recent years, but limitations associated to challenging cell genome edition, insufficient number production, the use of only autologous cells, and lack product standardization have limited its clinical use. The alternative generated vitro from human pluripotent stem (hPSCs) offers great advantages by providing a self-renewing source that can be readily genetically modified facilitate standardized...

10.3390/cells11244046 article EN cc-by Cells 2022-12-14

The success of inducing human pluripotent stem cells (hIPSC) offers new opportunities for cell-based therapy. Since B exert roles as effector and regulator immune responses in different clinical settings, we were interested generating from hIPSC. We differentiated embryonic (hESC) hIPSC into onto OP9 MS-5 stromal successively. overcame issues CD34 + CD43 hematopoietic progenitors with appropriate cytokine conditions emphasized the difficulties to generate proper progenitors. highlight CD31...

10.1371/journal.pone.0243769 article EN cc-by PLoS ONE 2020-12-15

SUMMARY Human trophoblast stem cells (hTSC) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the human placenta. However, access embryos first trimester placentas is limited thus preventing establishment of hTSC a variety genetic backgrounds associated with placental disorders. In present study, we show that can be generated numerous using post-natal via two alternative methods: (I) somatic cell reprogramming adult fibroblasts Yamanaka...

10.1101/2020.09.15.298257 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-09-15

ABSTRACT Immunotherapy using primary T cells has revolutionized medical care in some pathologies recent years but limitations associated to challenging cell genome edition, insufficient number production, the use of only autologous and lack product standardization have limited its uses clinic. The alternative generated vitro from human pluripotent stem (hPSCs) offers great advantages by providing a self-renewing source that can be readily genetically modified facilitate standardized...

10.1101/2021.09.02.458682 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2021-09-05

ABSTRACT Although described in the 70’s, CD8 + regulatory T cells (Tregs) remain incompletely understood and to date, although several markers are used define them, they poorly defined. The identification of reliable consistent markers, as it was done for CD4 Tregs, remains an urgent task a challenge advance our understanding. Herein, we analyzed total using single cell CITEseq VDJ receptor sequencing utilizing previously identify particular CD45RC by team others divide pro-inflammatory...

10.1101/2023.12.13.571475 preprint EN cc-by-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-12-14

One major goal in transplantation is to develop novel specific and non-toxic anti-rejection immunotherapies. Strategies based on regulatory T cells (Tregs) are promising prevent graft rejection. Our group has shown that rat human CD8+CD45RClow/- Tregs display significant suppressive function. The team also cell therapy using was efficient rejection GVHD humanized NSG mice models. However, the heterogeneity of population important from a phenotypic point view, suggesting either fraction...

10.1097/01.tp.0000698404.97541.79 article EN Transplantation 2020-08-28

Abstract Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently its expression by CD8+ rat model of transplantation tolerance activated FOXP3+ CD4+ human healthy individuals. However, role autoimmunity potential diseases remain be determined. Here report that the absence Il34 -/- rodents leads an unstable phenotype, production...

10.1101/2022.02.04.479184 preprint EN cc-by-nc bioRxiv (Cold Spring Harbor Laboratory) 2022-02-06

CD8+ regulatory T cells (Tregs) were the first suppressive reported in 1970, but they put aside for years due to a lack of markers properly define them. Our team demonstrated that Tregs identified by low and/or negative expression CD45RC, one isoforms CD45 molecule, show potent activity vitro and vivo, while expressing high levels CD45RC do not. Herein, we addressed heterogeneity within CD8+CD45RClow/- new markers. We performed single cell RNA-sequencing on more than 10000 non-stimulated 3...

10.1097/01.tp.0000887496.59618.9b article EN Transplantation 2022-09-01
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