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Article ; Online: Are the B cells cast with the leading part in the Sjogren's syndrome scenario?

Pers, J O / Youinou, P

2014 Volume 20, Issue 6, Page(s) 529–537

Abstract: The autoimmune exocrinopathy Sjögren's syndrome (SS) is characterized by mononuclear cell (MNC) infiltrates of exocrine glands and overactivity of B lymphocytes. Although T cells have long been perceived as the prime effectors, increasing evidence ... ...

Abstract	The autoimmune exocrinopathy Sjögren's syndrome (SS) is characterized by mononuclear cell (MNC) infiltrates of exocrine glands and overactivity of B lymphocytes. Although T cells have long been perceived as the prime effectors, increasing evidence indicates that the key role is rather served by B cells. Among related abnormalities are rheumatoid factor (RF), anti-SSA/Ro, and anti-SSB/La antibodies (Ab). Also, supporting this view is our finding of an increase in the number of circulating naïve mature B (Bm) cells, with a reciprocal decrease in that of memory B cells. Furthermore, a ratio of Bm2-plus-Bm2' cells to early Bm5-plus-late Bm5 above 5 is diagnostic. This variation partly reflects the migration of active memory B cells into the exocrine glands of the patients, as well as into their skin. More recently, the B-cell-activating factor of the TNF family (BAFF) has been endorsed with a pivotal role in B-cell survival and hence implicated in the pathogenesis of autoimmunity. In practice, B cells have turned quite attractive as a target for biotherapy. For example, treatment with anti-CD20 Ab has afforded some benefits in this disease, while BAFF blockers are still on the way, but should expand our armamentarium for treating SS. With such B-cell-directed biotherapies in mind, we delineate herein the distinguishing traits of B lymphocytes in SS.
MeSH term(s)	Antigens, CD/analysis ; B-Lymphocyte Subsets/chemistry ; B-Lymphocyte Subsets/classification ; B-Lymphocyte Subsets/immunology ; B-Lymphocyte Subsets/metabolism ; Cytokines/metabolism ; Humans ; Lymphocyte Count ; Salivary Glands/immunology ; Salivary Glands/pathology ; Sjogren's Syndrome/diagnosis ; Sjogren's Syndrome/drug therapy ; Sjogren's Syndrome/immunology
Chemical Substances	Antigens, CD ; Cytokines
Language	English
Publishing date	2014-09
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	1290529-x
ISSN	1601-0825 ; 1354-523X
ISSN (online)	1601-0825
ISSN	1354-523X
DOI	10.1111/odi.12153
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Zs.A 4427: Show issues

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Article: Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety.

Webster, Addison N / Becker, Jordan J / Li, Chia / Schwalbe, Dana C / Kerspern, Damien / Karolczak, Eva O / Godschall, Elizabeth N / Belmont-Rausch, Dylan Matthew / Pers, Tune H / Lutas, Andrew / Habib, Naomi / Güler, Ali D / Krashes, Michael J / Campbell, John N

bioRxiv : the preprint server for biology

2023

Abstract: Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. GLP-1RAs inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate ... ...

Abstract	Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. GLP-1RAs inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc) but only indirectly, implicating synaptic afferents to AgRP neurons. To investigate, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics. Applying this method to AgRP neurons in mice predicts 21 afferent subtypes in the mediobasal and paraventricular hypothalamus. Among these are
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.31.564990
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Article ; Online: B lymphocytes in nonorgan-specific autoimmune diseases: implications for therapy.

Youinou, P / Pers, J-O

Lupus

2012 Volume 21, Issue 13, Page(s) 1375–1377

MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Autoimmune Diseases/drug therapy ; Autoimmune Diseases/immunology ; Autoimmunity/drug effects ; B-Cell Activating Factor/metabolism ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; CD5 Antigens/metabolism ; Humans ; Immunosuppressive Agents/therapeutic use ; Signal Transduction ; Tumor Necrosis Factor Ligand Superfamily Member 13/metabolism
Chemical Substances	Antibodies, Monoclonal ; B-Cell Activating Factor ; CD5 Antigens ; Immunosuppressive Agents ; Tumor Necrosis Factor Ligand Superfamily Member 13
Language	English
Publishing date	2012-11
Publishing country	England
Document type	Editorial
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/0961203312460901
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Zs.A 3717: Show issues

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Article ; Online: CD5 and B lymphocyte responses: multifaceted effects through multitudes of pathways and channels.

Taher, Taher E / Bystrom, Jonas / Mignen, Olivier / Pers, Jacques-Olivier / Renaudineau, Yves / Mageed, Rizgar A

Cellular & molecular immunology

2020 Volume 17, Issue 11, Page(s) 1201–1203

MeSH term(s)	B-Lymphocytes/immunology ; CD5 Antigens/metabolism ; Cell Line, Tumor ; Cell Survival ; Humans ; Interleukin-10/metabolism ; Models, Biological ; Signal Transduction ; T-Lymphocytes/immunology
Chemical Substances	CD5 Antigens ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2020-07-01
Publishing country	China
Document type	Letter
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/s41423-020-0490-z
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Zs.A 6681: Show issues

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Article ; Online: Prise en charge des patients sous anticorps thérapeutiques en odontostomatologie.

Demoersman, J / Soueidan, A / Corre, P / Pers, J O

Revue de stomatologie, de chirurgie maxillo-faciale et de chirurgie orale

2014 Volume 115, Issue 3, Page(s) 152–163

Abstract: Immunotherapies, particularly therapeutic antibodies, are increasingly used in the treatment of many autoimmune or oncological diseases. Patients treated with therapeutic antibodies may present with an increased risk of infection or of osteonecrosis of ... ...

Title translation	Managing patients with therapeutic antibodies in odontostomatology.
Abstract	Immunotherapies, particularly therapeutic antibodies, are increasingly used in the treatment of many autoimmune or oncological diseases. Patients treated with therapeutic antibodies may present with an increased risk of infection or of osteonecrosis of the jaws (ONJ). There is currently no consensus on the management of patients treated with therapeutic antibodies. These treatments are mainly used in hospitals, but they have been increasingly prescribed in ambulatory treatment for patients undergoing oral care. It is therefore important to establish therapeutic precautions for these patients. We had for aim to describe these antibody therapies, their indications, their potentially adverse effects in the oral cavity and to review the latest recommendations.
MeSH term(s)	Antibodies/adverse effects ; Autoimmune Diseases/complications ; Autoimmune Diseases/therapy ; Humans ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Neoplasms/complications ; Neoplasms/therapy ; Oral Medicine/methods ; Practice Guidelines as Topic ; Stomatognathic Diseases/diagnosis ; Stomatognathic Diseases/etiology ; Stomatognathic Diseases/therapy
Chemical Substances	Antibodies
Language	French
Publishing date	2014-06
Publishing country	France
Document type	English Abstract ; Journal Article ; Review
ISSN	2213-6541
ISSN (online)	2213-6541
DOI	10.1016/j.revsto.2014.03.004
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Article ; Online: Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis.

Hundahl, Cecilie / Kotzbeck, Petra / Burm, Hayley B / Christiansen, Søren H / Torz, Lola / Helge, Aske W / Madsen, Martin P / Ratner, Cecilia / Serup, Annette K / Thompson, Jonatan J / Eichmann, Thomas O / Pers, Tune H / Woldbye, David P D / Piomelli, Daniele / Kiens, Bente / Zechner, Rudolf / Skov, Louise J / Holst, Birgitte

Molecular metabolism

2021 Volume 47, Page(s) 101174

Abstract: Objective: The goal of this study was to investigate the importance of central hormone-sensitive lipase (HSL) expression in the regulation of food intake and body weight in mice to clarify whether intracellular lipolysis in the mammalian hypothalamus ... ...

Abstract	Objective: The goal of this study was to investigate the importance of central hormone-sensitive lipase (HSL) expression in the regulation of food intake and body weight in mice to clarify whether intracellular lipolysis in the mammalian hypothalamus plays a role in regulating appetite. Methods: Using pharmacological and genetic approaches, we investigated the role of HSL in the rodent brain in the regulation of feeding and energy homeostasis under basal conditions during acute stress and high-fat diet feeding. Results: We found that HSL, a key enzyme in the catabolism of cellular lipid stores, is expressed in the appetite-regulating centers in the hypothalamus and is activated by acute stress through a mechanism similar to that observed in adipose tissue and skeletal muscle. Inhibition of HSL in rodent models by a synthetic ligand, global knockout, or brain-specific deletion of HSL prevents a decrease in food intake normally seen in response to acute stress and is associated with the increased expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP). Increased food intake can be reversed by adeno-associated virus-mediated reintroduction of HSL in neurons of the mediobasal hypothalamus. Importantly, metabolic stress induced by a high-fat diet also enhances the hyperphagic phenotype of HSL-deficient mice. Specific deletion of HSL in the ventromedial hypothalamic nucleus (VMH) or AgRP neurons reveals that HSL in the VMH plays a role in both acute stress-induced food intake and high-fat diet-induced obesity. Conclusions: Our results indicate that HSL activity in the mediobasal hypothalamus is involved in the acute reduction in food intake during the acute stress response and sensing of a high-fat diet.
MeSH term(s)	Agouti-Related Protein/metabolism ; Animals ; Appetite/physiology ; Body Weight ; Diet, High-Fat/adverse effects ; Eating ; Energy Metabolism ; Female ; Homeostasis ; Hyperphagia/metabolism ; Hypothalamus/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; Neuropeptide Y/metabolism ; Obesity/metabolism ; RNA Splicing Factors ; Sterol Esterase/genetics ; Sterol Esterase/metabolism ; Stress, Physiological/genetics ; Transcriptome
Chemical Substances	Agouti-Related Protein ; Neuropeptide Y ; RNA Splicing Factors ; Sf1 protein, mouse ; Sterol Esterase (EC 3.1.1.13)
Language	English
Publishing date	2021-02-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2021.101174
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Article ; Online: GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity.

Falk, Sarah / Petersen, Jonas / Svendsen, Charlotte / Romero-Leguizamón, Cesar R / Jørgensen, Søren Heide / Krauth, Nathalie / Ludwig, Mette Q / Lundø, Kathrine / Roostalu, Urmas / Skovbjerg, Grethe / Nielsen, Duy Anh Gurskov / Ejdrup, Aske Lykke / Pers, Tune H / Dmytriyeva, Oksana / Hecksher-Sørensen, Jacob / Gether, Ulrik / Kohlmeier, Kristi A / Clemmensen, Christoffer

Cell reports

2023 Volume 42, Issue 5, Page(s) 112466

Abstract: Glucagon-like peptide-1 receptor (GLP-1R) agonists promote nicotine avoidance. Here, we show that the crosstalk between GLP-1 and nicotine extends beyond effects on nicotine self-administration and can be exploited pharmacologically to amplify the anti- ... ...

Abstract	Glucagon-like peptide-1 receptor (GLP-1R) agonists promote nicotine avoidance. Here, we show that the crosstalk between GLP-1 and nicotine extends beyond effects on nicotine self-administration and can be exploited pharmacologically to amplify the anti-obesity effects of both signals. Accordingly, combined treatment with nicotine and the GLP-1R agonist, liraglutide, inhibits food intake and increases energy expenditure to lower body weight in obese mice. Co-treatment with nicotine and liraglutide gives rise to neuronal activity in multiple brain regions, and we demonstrate that GLP-1R agonism increases excitability of hypothalamic proopiomelanocortin (POMC) neurons and dopaminergic neurons in the ventral tegmental area (VTA). Further, using a genetically encoded dopamine sensor, we reveal that liraglutide suppresses nicotine-induced dopamine release in the nucleus accumbens in freely behaving mice. These data support the pursuit of GLP-1R-based therapies for nicotine dependence and encourage further evaluation of combined treatment with GLP-1R agonists and nicotinic receptor agonists for weight loss.
MeSH term(s)	Mice ; Animals ; Glucagon-Like Peptide 1/pharmacology ; Liraglutide/pharmacology ; Nicotine/pharmacology ; Dopamine ; Obesity/drug therapy ; Obesity/metabolism
Chemical Substances	Glucagon-Like Peptide 1 (89750-14-1) ; Liraglutide (839I73S42A) ; Nicotine (6M3C89ZY6R) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112466
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Article ; Online: Defective DNA methylation in salivary gland epithelial acini from patients with Sjögren's syndrome is associated with SSB gene expression, anti-SSB/LA detection, and lymphocyte infiltration.

Konsta, O D / Le Dantec, C / Charras, A / Cornec, D / Kapsogeorgou, E K / Tzioufas, A G / Pers, J O / Renaudineau, Y

Journal of autoimmunity

2016 Volume 68, Page(s) 30–38

Abstract: The pathogenesis of primary Sjögren's syndrome (pSS) is complex, in part due to DNA methylation abnormalities. This study was undertaken to evaluate the importance of global DNA methylation ((5m)C) as determined in minor salivary glands (MSG) from well ... ...

Abstract	The pathogenesis of primary Sjögren's syndrome (pSS) is complex, in part due to DNA methylation abnormalities. This study was undertaken to evaluate the importance of global DNA methylation ((5m)C) as determined in minor salivary glands (MSG) from well characterized pSS patients. Twenty-two pSS patients and ten controls were selected, and MSG were stained with anti-(5m)C, anti-(5m)C/anti-cytokeratin (KRT)19, or with anti-SSB/La antibodies (Ab). The DNA methylation status at the SSB gene promoter P1 and P1' was evaluated by methylation-sensitive restriction enzymes (MSRE) coupled with PCR. The effect of the DNA demethylating drug 5 azacytidine (5-Aza) was tested in the human salivary gland (HSG) cell line. In pSS, the reduction of global DNA methylation ((5m)C) was associated with lymphocyte infiltration, the emergence of (5m)C(low) and KRT19(high) acini, and the detection of circulating anti-SSB/La Ab, but not with disease activity (ESSDAI). Next, treating HSG cells with 5-Aza was effective in inducing SSB expression. Finally in pSS patients positive for anti-SSB/La Ab, we further observed DNA demethylation at the SSB gene promoter P1 with consequent SSB overexpression at both the transcriptional and protein levels in salivary gland epithelial cells. In conclusion, our results highlight the importance of DNA methylation in the pathophysiology of pSS and to the emergence of anti-SSB/La Ab.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Antinuclear/immunology ; Azacitidine/pharmacology ; DNA Methylation ; Female ; Gene Expression Regulation/drug effects ; Humans ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Lymphocytes/pathology ; Male ; Middle Aged ; Phosphoproteins/genetics ; Phosphoproteins/immunology ; Salivary Glands, Minor/immunology ; Salivary Glands, Minor/metabolism ; Sjogren's Syndrome/diagnosis ; Sjogren's Syndrome/genetics ; Sjogren's Syndrome/immunology ; Young Adult
Chemical Substances	Antibodies, Antinuclear ; La protein, human ; Phosphoproteins ; SS-B antibodies ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2016-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2015.12.002
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Zs.A 2368: Show issues

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Article ; Online: Intravenous immunoglobulin induces anergy statelike of auto-reactive B lymphocytes in Sjögren's syndrome.

Seite, J-F / Pers, J-O / Youinou, P / Hillion, S

Bulletin du Groupement international pour la recherche scientifique en stomatologie & odontologie

2011 Volume 50, Issue 2, Page(s) 16–17

MeSH term(s)	B-Lymphocytes ; Clonal Anergy ; Humans ; Immunoglobulins, Intravenous ; Sjogren's Syndrome
Chemical Substances	Immunoglobulins, Intravenous
Language	English
Publishing date	2011-11-22
Publishing country	Belgium
Document type	Journal Article
ZDB-ID	604450-5
ISSN	1647-1377 ; 0250-4693
ISSN (online)	1647-1377
ISSN	0250-4693
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Article ; Online: Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature.

Teruel, María / Barturen, Guillermo / Martínez-Bueno, Manuel / Castellini-Pérez, Olivia / Barroso-Gil, Miguel / Povedano, Elena / Kerick, Martin / Català-Moll, Francesc / Makowska, Zuzanna / Buttgereit, Anne / Pers, Jacques-Olivier / Marañón, Concepción / Ballestar, Esteban / Martin, Javier / Carnero-Montoro, Elena / Alarcón-Riquelme, Marta E

Scientific reports

2021 Volume 11, Issue 1, Page(s) 23292

Abstract: Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By ... ...

Abstract	Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.
MeSH term(s)	Autoantibodies ; DNA Methylation/genetics ; Epigenomics ; Female ; Gene Expression/genetics ; Gene Expression Regulation/genetics ; Genetic Variation ; HLA Antigens/genetics ; Humans ; Interferons/genetics ; Male ; Sjogren's Syndrome/etiology ; Sjogren's Syndrome/genetics ; Sjogren's Syndrome/immunology
Chemical Substances	Autoantibodies ; HLA Antigens ; Interferons (9008-11-1)
Language	English
Publishing date	2021-12-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-01324-0
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