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Article ; Online: Antigen specific activation of cytotoxic CD8

Friot, Adèle / Djebali, Sophia / Valsesia, Séverine / Parroche, Peggy / Dubois, Maxence / Baude, Jessica / Vandenesch, François / Marvel, Jacqueline / Leverrier, Yann

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1245299

Abstract: Staphylococcus ... ...

Abstract	Staphylococcus aureus
MeSH term(s)	Mice ; Animals ; CD8-Positive T-Lymphocytes ; Staphylococcus aureus ; T-Lymphocytes, Cytotoxic ; Epitopes, T-Lymphocyte ; Dendritic Cells
Chemical Substances	Epitopes, T-Lymphocyte
Language	English
Publishing date	2023-10-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1245299
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Article ; Online: Generation of a C57BL/6J mouse strain expressing the CD45.1 epitope to improve hematopoietic stem cell engraftment and adoptive cell transfer experiments.

Laubreton, Daphné / Djebali, Sophia / Angleraux, Céline / Chain, Benny / Dubois, Maxence / Henry, Farida / Leverrier, Yann / Teixeira, Marie / Markossian, Suzy / Marvel, Jacqueline

Lab animal

2023 Volume 52, Issue 12, Page(s) 324–331

Abstract: Adoptive cell transfer between genetically identical hosts relies on the use of a congenic marker to distinguish the donor cells from the host cells. CD45, a glycoprotein expressed by all hematopoietic cells, is one of the main congenic markers used ... ...

Abstract	Adoptive cell transfer between genetically identical hosts relies on the use of a congenic marker to distinguish the donor cells from the host cells. CD45, a glycoprotein expressed by all hematopoietic cells, is one of the main congenic markers used because its two isoforms, CD45.1 and CD45.2, can be discriminated by flow cytometry. As a consequence, C57BL/6J (B6; CD45.2) and B6.SJL-Ptprc
MeSH term(s)	Mice ; Animals ; Mice, Inbred C57BL ; CD8-Positive T-Lymphocytes ; Epitopes ; Hematopoietic Stem Cells ; Mice, Inbred Strains ; Adoptive Transfer
Chemical Substances	Epitopes
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ISSN	1548-4475
ISSN (online)	1548-4475
DOI	10.1038/s41684-023-01275-1
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Article ; Online: Exogenous IL-2 delays memory precursors generation and is essential for enhancing memory cells effector functions.

Wang, Shaoying / Prieux, Margaux / de Bernard, Simon / Dubois, Maxence / Laubreton, Daphne / Djebali, Sophia / Zala, Manon / Arpin, Christophe / Genestier, Laurent / Leverrier, Yann / Gandrillon, Olivier / Crauste, Fabien / Jiang, Wenzheng / Marvel, Jacqueline

iScience

2024 Volume 27, Issue 4, Page(s) 109411

Abstract: To investigate the impact of paracrine IL-2 signals on memory precursor (MP) cell differentiation, we activated CD8 T ... ...

Abstract	To investigate the impact of paracrine IL-2 signals on memory precursor (MP) cell differentiation, we activated CD8 T cell
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109411
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Article ; Online: Combining SARS-CoV-2 interferon-gamma release assay with humoral response assessment to define immune memory profiles.

European journal of immunology

2024 , Page(s) e2451035

Abstract: Objectives: In the post-SARS-CoV-2 pandemic era, "breakthrough infections" are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti-Spike (S) ... ...

Abstract	Objectives: In the post-SARS-CoV-2 pandemic era, "breakthrough infections" are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti-Spike (S) immunoglobulin-G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T-cell response assessment to enhance the definition of immune memory profile. Methods: SARS-CoV-2 interferon-gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti-receptor-binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated. Results: Close to 40% of our samples were exclusively IGRA-positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long-lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti-receptor-binding domain IgG and IGRA levels tended to reduce it. Conclusion: The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level.
Language	English
Publishing date	2024-04-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202451035
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Article ; Online: Loss of Pla2r1 decreases cellular senescence and age-related alterations caused by aging and Western diets.

Massemin, Amélie / Goehrig, Delphine / Flaman, Jean-Michel / Jaber, Sara / Griveau, Audrey / Djebali, Sophia / Marcos, Elisabeth / Payen, Léa / Marvel, Jacqueline / Parent, Romain / Adnot, Serge / Bertolino, Philippe / Rieusset, Jennifer / Tortereau, Antonin / Vindrieux, David / Bernard, David

Aging cell

2023 Volume 22, Issue 11, Page(s) e13971

Abstract: Cellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of ... ...

Abstract	Cellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of senescent cells promotes many age-related alterations and diseases. In this study, we investigated the role of the pro-senescent phospholipase A2 receptor 1 (PLA2R1) in regulating some age-related alterations in old mice and in mice subjected to a Western diet, whereas aged wild-type mice displayed a decreased ability to regulate their glycemia during glucose and insulin tolerance tests, aged Pla2r1 knockout (KO) mice efficiently regulated their glycemia and displayed fewer signs of aging. Loss of Pla2r1 was also found protective against the deleterious effects of a Western diet. Moreover, these Pla2r1 KO mice were partially protected from diet-induced senescent cell accumulation, steatosis, and fibrosis. Together these results support that Pla2r1 drives several age-related alterations, especially in the liver, arising during aging or through a Western diet.
MeSH term(s)	Animals ; Mice ; Aging/genetics ; Cellular Senescence/genetics ; Diet, Western ; Mice, Knockout ; Telomere Shortening
Chemical Substances	Pla2r1 protein, mouse
Language	English
Publishing date	2023-09-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13971
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Article ; Online: OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza.

Del Campo, Judith / Bouley, Julien / Chevandier, Marion / Rousset, Carine / Haller, Marjorie / Indalecio, Alice / Guyon-Gellin, Delphine / Le Vert, Alexandre / Hill, Fergal / Djebali, Sophia / Leverrier, Yann / Marvel, Jacqueline / Combadière, Béhazine / Nicolas, Florence

Frontiers in immunology

2021 Volume 12, Page(s) 678483

Abstract: Tissue-resident memory (TRM) CD8+ T-cells play a crucial role in the protection against influenza infection but remain difficult to elicit using recombinant protein vaccines. OVX836 is a recombinant protein vaccine, obtained by the fusion of the DNA ... ...

Abstract	Tissue-resident memory (TRM) CD8+ T-cells play a crucial role in the protection against influenza infection but remain difficult to elicit using recombinant protein vaccines. OVX836 is a recombinant protein vaccine, obtained by the fusion of the DNA sequence of the influenza A nucleoprotein (NP) to the DNA sequence of the OVX313 heptamerization domain. We previously demonstrated that OVX836 provides broad-spectrum protection against influenza viruses. Here, we show that OVX836 intramuscular (IM) immunization induces higher numbers of NP-specific IFNγ-producing CD8+ T-cells in the lung, compared to mutant NP (NPm) and wild-type NP (NPwt), which form monomeric and trimeric structures, respectively. OVX836 induces cytotoxic CD8+ T-cells and high frequencies of lung TRM CD8+ T-cells, while inducing solid protection against lethal influenza virus challenges for at least 90 days. Adoptive transfer experiments demonstrated that protection against diverse influenza subtypes is mediated by NP-specific CD8+ T-cells isolated from the lung and spleen following OVX836 vaccination. OVX836 induces a high number of NP-specific lung CD8+ TRM-cells for long-term protection against influenza viruses.
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Enzyme-Linked Immunospot Assay ; Humans ; Immunization ; Immunologic Memory ; Influenza A virus/immunology ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Interferon-gamma/metabolism ; Lung/immunology ; Lung/metabolism ; Lung/virology ; Mice ; Nucleocapsid Proteins/chemistry ; Nucleocapsid Proteins/immunology ; Organ Specificity/immunology
Chemical Substances	Antibodies, Viral ; Influenza Vaccines ; NP protein, Influenza A virus ; Nucleocapsid Proteins ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2021-06-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.678483
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Article ; Online: mTOR Activation Underlies Enhanced B Cell Proliferation and Autoimmunity in PrkcdG510S/G510S Mice.

Moreews, Marion / Mathieu, Anne-Laure / Pouxvielh, Kevin / Reuschlé, Quentin / Drouillard, Annabelle / Dessay, Pénélope / Meignien, Marie / Zhang, Jiang / Fallone, Lucie / Rousseaux, Noëmi / Ainouze, Michelle / Rey, Amaury / Omarjee, Ommar / Decembre, Elodie / Lenief, Vanina / Djebali, Sophia / Thaunat, Olivier / Dreux, Marlène / Genestier, Laurent /

Defrance, Thierry / Soulas-Sprauel, Pauline / Marçais, Antoine / Walzer, Thierry / Belot, Alexandre

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 210, Issue 9, Page(s) 1209–1221

Abstract: Autosomal recessive PRKCD deficiency has previously been associated with the development of systemic lupus erythematosus in human patients, but the mechanisms underlying autoimmunity remain poorly understood. We introduced the Prkcd G510S mutation that ... ...

Abstract	Autosomal recessive PRKCD deficiency has previously been associated with the development of systemic lupus erythematosus in human patients, but the mechanisms underlying autoimmunity remain poorly understood. We introduced the Prkcd G510S mutation that we previously associated to a Mendelian cause of systemic lupus erythematosus in the mouse genome, using CRISPR-Cas9 gene editing. PrkcdG510S/G510S mice recapitulated the human phenotype and had reduced lifespan. We demonstrate that this phenotype is linked to a B cell-autonomous role of Prkcd. A detailed analysis of B cell activation in PrkcdG510S/G510S mice shows an upregulation of the PI3K/mTOR pathway after the engagement of the BCR in these cells, leading to lymphoproliferation. Treatment of mice with rapamycin, an mTORC1 inhibitor, significantly improves autoimmune symptoms, demonstrating in vivo the deleterious effect of mTOR pathway activation in PrkcdG510S/G510S mice. Additional defects in PrkcdG510S/G510S mice include a decrease in peripheral mature NK cells that might contribute to the known susceptibility to viral infections of patients with PRKCD mutations.
MeSH term(s)	Humans ; Animals ; Mice ; Autoimmunity ; Lupus Erythematosus, Systemic ; TOR Serine-Threonine Kinases/metabolism ; B-Lymphocytes ; Cell Proliferation
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.11.1) ; MTOR protein, human (EC 2.7.1.1)
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200818
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Article: Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny.

Crauste, Fabien / Mafille, Julien / Boucinha, Lilia / Djebali, Sophia / Gandrillon, Olivier / Marvel, Jacqueline / Arpin, Christophe

Cell systems

2017 Volume 4, Issue 3, Page(s) 306–317.e4

Abstract: Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory ... ...

Abstract	Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway. Moreover, our mathematical model allows long-term prediction of memory cell numbers from a few early experimental measurements. Our work thus provides a phenotypic means to identify effector and memory cells, as well as a mathematical framework to investigate their genealogy and to predict the outcome of immunization regimens in terms of memory cell numbers generated.
MeSH term(s)	Animals ; B-Lymphocyte Subsets/classification ; Biological Ontologies ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/physiology ; Cell Differentiation/immunology ; Cell Line ; Immunologic Memory/immunology ; Ki-67 Antigen/physiology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Phenotype ; Proto-Oncogene Proteins c-bcl-2
Chemical Substances	Ki-67 Antigen ; MKI67 protein, human ; Proto-Oncogene Proteins c-bcl-2
Language	English
Publishing date	2017-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2405-4712
ISSN	2405-4712
DOI	10.1016/j.cels.2017.01.014
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Article ; Online: Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging.

Ziegler, Dorian V / Vindrieux, David / Goehrig, Delphine / Jaber, Sara / Collin, Guillaume / Griveau, Audrey / Wiel, Clotilde / Bendridi, Nadia / Djebali, Sophia / Farfariello, Valerio / Prevarskaya, Natacha / Payen, Léa / Marvel, Jacqueline / Aubert, Sébastien / Flaman, Jean-Michel / Rieusset, Jennifer / Martin, Nadine / Bernard, David

Nature communications

2021 Volume 12, Issue 1, Page(s) 720

Abstract: Cellular senescence is induced by stresses and results in a stable proliferation arrest accompanied by a pro-inflammatory secretome. Senescent cells accumulate during aging, promoting various age-related pathologies and limiting lifespan. The endoplasmic ...

Abstract	Cellular senescence is induced by stresses and results in a stable proliferation arrest accompanied by a pro-inflammatory secretome. Senescent cells accumulate during aging, promoting various age-related pathologies and limiting lifespan. The endoplasmic reticulum (ER) inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) calcium-release channel and calcium fluxes from the ER to the mitochondria are drivers of senescence in human cells. Here we show that Itpr2 knockout (KO) mice display improved aging such as increased lifespan, a better response to metabolic stress, less immunosenescence, as well as less liver steatosis and fibrosis. Cellular senescence, which is known to promote these alterations, is decreased in Itpr2 KO mice and Itpr2 KO embryo-derived cells. Interestingly, ablation of ITPR2 in vivo and in vitro decreases the number of contacts between the mitochondria and the ER and their forced contacts induce premature senescence. These findings shed light on the role of contacts and facilitated exchanges between the ER and the mitochondria through ITPR2 in regulating senescence and aging.
MeSH term(s)	Animals ; Calcium/metabolism ; Cellular Senescence/physiology ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/ultrastructure ; Female ; Fibroblasts ; HEK293 Cells ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/genetics ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Longevity/physiology ; Male ; Mice ; Mice, Knockout ; Microscopy, Confocal ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; RNA, Small Interfering ; Refractory Period, Electrophysiological ; Single-Cell Analysis
Chemical Substances	ITPR2 protein, human ; Inositol 1,4,5-Trisphosphate Receptors ; Ip3r2 protein, mouse ; RNA, Small Interfering ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-02-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-20993-z
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Article ; Online: PLA2R1 promotes DNA damage and inhibits spontaneous tumor formation during aging.

Huna, Anda / Griveau, Audrey / Vindrieux, David / Jaber, Sara / Flaman, Jean-Michel / Goehrig, Delphine / Azzi, Lamia / Médard, Jean-Jacques / Djebali, Sophia / Hernandez-Vargas, Hector / Dante, Robert / Payen, Léa / Marvel, Jacqueline / Bertolino, Philippe / Aubert, Sébastien / Dubus, Pierre / Bernard, David

Cell death & disease

2021 Volume 12, Issue 2, Page(s) 190

Abstract: Although aging is a major risk factor for most types of cancers, it is barely studied in this context. The transmembrane protein PLA2R1 (phospholipase A2 receptor) promotes cellular senescence, which can inhibit oncogene-induced tumor initiation. ... ...

Abstract	Although aging is a major risk factor for most types of cancers, it is barely studied in this context. The transmembrane protein PLA2R1 (phospholipase A2 receptor) promotes cellular senescence, which can inhibit oncogene-induced tumor initiation. Functions and mechanisms of action of PLA2R1 during aging are largely unknown. In this study, we observed that old Pla2r1 knockout mice were more prone to spontaneously develop a wide spectrum of tumors compared to control littermates. Consistently, these knockout mice displayed increased Parp1, a master regulator of DNA damage repair, and decreased DNA damage, correlating with large human dataset analysis. Forced PLA2R1 expression in normal human cells decreased PARP1 expression, induced DNA damage and subsequent senescence, while the constitutive expression of PARP1 rescued cells from these PLA2R1-induced effects. Mechanistically, PARP1 expression is repressed by a ROS (reactive oxygen species)-Rb-dependent mechanism upon PLA2R1 expression. In conclusion, our results suggest that PLA2R1 suppresses aging-induced tumors by repressing PARP1, via a ROS-Rb signaling axis, and inducing DNA damage and its tumor suppressive responses.
MeSH term(s)	Age Factors ; Aging/genetics ; Aging/metabolism ; Aging/pathology ; Animals ; Cell Line ; Cell Proliferation ; Cellular Senescence ; DNA Damage ; Databases, Genetic ; Female ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/prevention & control ; Poly (ADP-Ribose) Polymerase-1/genetics ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Reactive Oxygen Species/metabolism ; Receptors, Phospholipase A2/genetics ; Receptors, Phospholipase A2/metabolism ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Mice
Chemical Substances	PLA2R1 protein, human ; Pla2r1 protein, mouse ; Reactive Oxygen Species ; Receptors, Phospholipase A2 ; Retinoblastoma Protein ; PARP1 protein, human (EC 2.4.2.30) ; Parp1 protein, mouse (EC 2.4.2.30) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30)
Language	English
Publishing date	2021-02-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-021-03468-3
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