Celine S. Lages

Cincinnati Children's Hospital Medical Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Claire Chougnet

University of Cincinnati Medical Center

Alexander Miethke

University of Cincinnati Medical Center

Julia Simmons

University of Delaware

François D. Boussin

Université Paris Cité

Tiffany Shi

Cincinnati Children's Hospital Medical Center

Rebekah Karns

University of Cincinnati

David A. Hildeman

University of Cincinnati Medical Center

Wujuan Zhang

Cincinnati Children's Hospital Medical Center

Ewa Nowak

Commissariat à l'Énergie Atomique et aux Énergies Alternatives

Kenneth D.R. Setchell

Cincinnati Children's Hospital Medical Center

Cooperative Institutions

Cincinnati Children's Hospital Medical Center

University of Cincinnati

University of Cincinnati Medical Center

Inserm

Commissariat à l'Énergie Atomique et aux Énergies Alternatives

CEA Paris-Saclay - Etablissement de Fontenay-aux-roses

Children’s Institute

Université Paris-Saclay

Children's Hospital & Medical Center

Children's Medical Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Su.100. Increased Levels of Regulatory T-Cell Markers in Healthy Elderly Donors

Clinical Immunology (2006)

Celine S. Lages Paula A. Velilla Gregg Warshaw Bin Huang Claire Chougnet

10.1016/j.clim.2006.04.527

Cite

Citations (0)

Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

Oncogene (2000)

Stéphane Haı̈k Laurent Gauthier Christine Granotier Jean‐Michel Peyrin Celine S. Lages

Gliogenesis

Precursor cell

10.1038/sj.onc.1203596

Cite

Citations (65)

Homeostasis and function of regulatory T cells in aging

Current Opinion in Immunology (2012)

Jana Raynor Celine S. Lages Hesham M. Shehata David A. Hildeman Claire Chougnet

Homeostasis

10.1016/j.coi.2012.04.005

Cite

Citations (144)

Rôle et régulation de la telomerase

Celine S. Lages

Source

Cite

Citations (0)

Loss of phagocytic and antigen cross-presenting capacity in aging DCs is associated with mitochondrial dysfunction

The Journal of Immunology (2016)

Edith M. Janssen Robert Thacker Hesham M. Shehata Celine S. Lages Cassandra M. Hennies

Abstract Impaired functionality of dendritic cells (DCs) significantly contributes to decreased adaptive immune responses in aged hosts. The expression of MHC-peptide on the DC surface is the critical first step in T cell priming, but few studies have addressed the effect of aging on antigen (Ag) acquisition, processing, and presentation by DCs. Here we show that aged murine DCs were less efficient in the cross-presentation of cell-associated Ag and subsequently in the cross-priming of CD8+ T cells than their young counterparts. The decreased cross-presentation was associated with a reduction in the frequency of CD8αDCs and merocytic (CD8α-CD11b-)DCs that could endocytose cell-associated Ag, as well as the number and the size of the endocytosed particles in the DC that did internalize cell-associated materials. Mechanistically, phagocytic capacity has been associated with mitochondrial activity and membrane potential (Δψm). Aged DCs exhibited profound signs of mitochondrial dysfunction, illustrated by lower Δψm, reduced ATP turnover and coupling efficiency, decreased baseline oxidative phosphorylation (OXPHOS), and greater proton leak and ROS production. Mimicking the aged metabolic phenotype in young DCs by pharmacologic manipulation indicated that the reductions in Δψm and ATP impeded the phagocytic capacity while ROS interfered with a later step in the cross-presentation process. Conversely, in vitro scavenging of ROS partially restored cross-presentation by aged DCs. Together, these data suggest that improvement of aged DC functionality might be feasible in the elderly, by targeting metabolic dysfunction, or its downstream sequelae, thereby opening new avenues for enhancing vaccine efficiency in this population.

Cross-Presentation

Priming (agriculture)

Mitochondrial ROS

10.4049/jimmunol.196.supp.116.13

Cite

Citations (1)

Neural stem cells from mouse forebrain are contained in a population distinct from the ‘side population’

Journal of Neurochemistry (2006)

Marc‐André Mouthon Pierre Fouchet Céline Mathieu Karine Sii-Felice Etienne Olivier

Abstract Developing and adult forebrains contain neural stem cells (NSCs) but no marker is available to highly purify them. When analysed by flow cytometry, stem cells from various tissues are enriched in a ‘side population’ (SP) characterized by the exclusion of the fluorescent dye Hoechst 33342. Here, we characterize the SP in embryonic, neonatal and adult forebrains, as well as in neurosphere cultures and we have determined whether this SP could be a source of enriched NSCs. By using specific inhibitors, we found that the SP from embryonic forebrain results from the activity of the ABCG2 transporter, a characteristic of other stem cells, whereas the SP from adult forebrain probably results from the ABCB1 transporter. SP cells from embryonic and adult forebrains, however, expressed a range of cell surface markers more consistent with a haematopoietic/endothelial origin than with a neural origin; NSC markers were mostly expressed on cells outside the SP (in the main population, MP). Moreover, assays for NSC growth in vitro showed that SP cells from embryonic and adult forebrains did not generate NSC‐derived colonies, whereas the MP did. We thus conclude that NSCs from developing and adult forebrains are not contained in the SP contrary to stem cells from other tissues.

Neurosphere

Forebrain

10.1111/j.1471-4159.2006.04118.x

Cite

Citations (44)

Association of two clones allows for optimal detection of human FOXP3

Cytometry Part A (2010)

Pietro Presicce Maria E. Moreno‐Fernandez Celine S. Lages Kris I. Orsborn Claire Chougnet

Abstract FOXP3 is a key transcription factor expressed by regulatory T cells (Treg cells). However, differences in staining and analysis protocols have led to conflicting results. Moreover, the transient upregulation of FOXP3 that follows activation in non‐Treg cells renders the interpretation of FOXP3 data more difficult in humans than in mice. Human peripheral blood mononuclear cells (PBMCs), isolated CD25 − or CD25 + CD4 + T cells were stained with three different anti‐FOXP3 clones (PCH101, 206D, and 259D) alone or in combination, and using different permeabilization methods. FOXP3 expression was evaluated following T cell activation by several pathways. Gating based on a population that did not express FOXP3 (such as CD3 − CD4 − T cells) allowed for the optimal characterization of Treg cells. The 206D clone detected a lower percentage of cells than PCH101 or 259D. In contrast, 259D stained a population of activated T cells that PCH101 did not. Staining with two clones together consistently increased the proportion of FOXP3 + cells. However, it is likely that only the double positive cells are Treg cells, as they expressed the highest CD25 and lowest CD127 levels. Our results emphasize that the choice of staining protocol leads to very different results concerning the frequency of Treg cells in humans. A more consistent identification of these cells will improve the knowledge of their biology, particularly during disease processes. © 2010 International Society for Advancement of Cytometry

clone (Java method)

10.1002/cyto.a.20875

Cite

Citations (29)

Functional Regulatory T Cells Accumulate in Aged Hosts and Promote Chronic Infectious Disease Reactivation

The Journal of Immunology (2008)

Celine S. Lages Isabelle Suffia Paula A. Velilla Bin Huang Gregg Warshaw

Abstract Declines in immune function are well described in the elderly and are considered to contribute significantly to the disease burden in this population. Regulatory T cells (Tregs), a CD4+ T cell subset usually characterized by high CD25 expression, control the intensity of immune responses both in rodents and humans. However, because CD25 expression does not define all Tregs, especially in aged hosts, we characterized Tregs by the expression of FOXP3, a transcription factor crucial for Treg differentiation and function. The proportion of FOXP3+CD4+ Tregs increased in the blood of the elderly and the lymphoid tissues of aged mice. The expression of functional markers, such as CTLA-4 and GITR, was either preserved or increased on FOXP3+ Tregs from aged hosts, depending on the tissue analyzed. In vitro depletion of peripheral Tregs from elderly humans improves effector T cell responses in most subjects. Importantly, Tregs from old FoxP3-GFP knock-in mice were suppressive, exhibiting a higher level of suppression per cell than young Tregs. The increased proportion of Tregs in aged mice was associated with the spontaneous reactivation of chronic Leishmania major infection in old mice, likely because old Tregs efficiently suppressed the production of IFN-γ by effector T cells. Finally, in vivo depletion of Tregs in old mice attenuated disease severity. Accumulation of functional Tregs in aged hosts could therefore play an important role in the frequent reactivation of chronic infections that occurs in aging. Manipulation of Treg numbers and/or activity may be envisioned to enhance the control of infectious diseases in this fragile population.

Regulatory T cell

10.4049/jimmunol.181.3.1835

Cite

Citations (364)

Cholestasis alters polarization and suppressor function of hepatic regulatory T cells.

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Ramesh Kudira Zi F Yang Immaculeta Osuji Rebekah Karns Priya Bariya

Fibrosing cholangiopathies, including biliary atresia and primary sclerosing cholangitis, involve immune-mediated bile duct epithelial injury and hepatic bile acid (BA) retention (cholestasis). Regulatory T-cells (Tregs) can prevent auto-reactive lymphocyte activation, yet the effects of BA on this CD4 lymphocyte subset are unknown. Gene regulatory networks for hepatic CD4 lymphocytes in a murine cholestasis model revealed Tregs are polarized to Th17 during cholestasis. Following bile duct ligation, Stat3 deletion in CD4 lymphocytes preserved hepatic Treg responses. While pharmacological reduction of hepatic BA in MDR2-/- mice prompted Treg expansion and diminished liver injury, this improvement subsided with Treg depletion. A cluster of patients diagnosed with biliary atresia showed both increased hepatic Treg responses and improved 2-year native liver survival, supporting that Tregs might protect against neonatal bile duct obstruction. Together, these findings suggest liver BA determine Treg function and should be considered as a therapeutic target to restore protective hepatic immune responses.

Primary Sclerosing Cholangitis

Ursodeoxycholic acid

Regulatory T cell

10.1101/2024.05.17.594680

Cite

Citations (0)

Partial restoration of T‐cell function in aged mice by in vitro blockade of the PD‐1/ PD‐L1 pathway

Aging Cell (2010)

Celine S. Lages Ian Lewkowich Alyssa Sproles Marsha Wills‐Karp Claire Chougnet

Programmed cell death-1 (PD-1) is a newly characterized negative regulator of immune responses. The interaction of PD-1 with its ligands (PD-L1 and PD-L2) inhibits T-cell proliferation and cytokine production in young mice. Increased PD-1 expression has been described during chronic infections, inducing chronic activation of the immune system to control it. As aging is associated with chronic immune activation, PD-1 may contribute to age-associated T-cell dysfunction. Our data showed the following results in aged mice: (i) the number of PD-1-expressing T cells and the level of expression of PD-Ls was increased on dendritic cell subsets and T cells; (ii) PD-1(+) T cells were exhausted effector memory T cells, as shown by their lower level of CD127, CD25 and CD28, as well as their limited proliferative and cytokine-producing capacity; (iii) the expression of PD-1 was up-regulated after T-cell receptor-mediated activation of CD8(+) T cells, but not of CD4(+) T cells; (iv) blockade of the PD-1/PD-L1 pathway moderately improved the cytokine production of T cells from old mice but did not restore their proliferation; and (v) blockade of the PD-1/PD-L1 pathway did not restore function of PD-1(+) T cells; its effect appeared to be exclusively mediated by increased functionality of the PD-1(-) T cells. Our data thus suggest that blockade of the PD-1/PD-L1 is not likely to be efficient at restoring exhausted T-cell responses in aged hosts, although improving the responses of PD-1(-) T cells may prove to be a helpful strategy in enhancing primary responses.

Interleukin-7 receptor

Memory T cell

ZAP70

10.1111/j.1474-9726.2010.00611.x

Cite

Citations (113)