Enric Esplugues, PhD
Research & Publications
Biography
Locations
Research Summary
Inflammation is a very important component of the host response to infections and tumors. However, excessive inflammation may lead to a variety of pathological states, including different autoimmune disorders. The main interest of our lab is focused on understanding the cellular and molecular basis that lead to the induction, development and resolution of inflammatory disorders that are caused by the dysfunctions of the innate and/or the adaptive immune system. In particular, we are interested in the study of the TH17 cells, a recently identified CD4+ T cell subset distinct from T helper type 1 (TH1) and T helper type 2 (TH2) cells. TH17 cells can drive antigen specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis. The factors that are needed for the generation of TH17 cells have been well characterized. However, where and how the immune system controls TH17 cells in vivo is one of our major interests. To address these questions, our laboratory employs a wide range of experimental techniques to get insight from epigenetics (FISH, 3C, ChIP, EMSA, DHA, genome wide gene expression analyses…) to the whole animal level (genetic approaches including conditional targeting and generation of different reporter mice).
Coauthors
Research Interests
Autoimmune Diseases; Immune System Diseases; Autoimmunity
Public Health Interests
Cancer; Nutrition
Selected Publications
- SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replicationMeseguer S, Rubio M, Lainez B, Pérez-Benavente B, Pérez-Moraga R, Romera-Giner S, García-García F, Martinez-Macias O, Cremades A, Iborra F, Candelas-Rivera O, Almazan F, Esplugues E. SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication. Frontiers In Microbiology 2023, 14: 1066493. PMID: 36876111, PMCID: PMC9978209, DOI: 10.3389/fmicb.2023.1066493.
- The induction and function of the anti-inflammatory fate of TH17 cellsXu H, Agalioti T, Zhao J, Steglich B, Wahib R, Vesely MCA, Bielecki P, Bailis W, Jackson R, Perez D, Izbicki J, Licona-Limón P, Kaartinen V, Geginat J, Esplugues E, Tolosa E, Huber S, Flavell RA, Gagliani N. The induction and function of the anti-inflammatory fate of TH17 cells. Nature Communications 2020, 11: 3334. PMID: 32620760, PMCID: PMC7335205, DOI: 10.1038/s41467-020-17097-5.
- Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial InfectionVesely M, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limón P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA. Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell 2019, 178: 1176-1188.e15. PMID: 31442406, PMCID: PMC7057720, DOI: 10.1016/j.cell.2019.07.032.
- Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progressionCalcinotto A, Brevi A, Chesi M, Ferrarese R, Garcia Perez L, Grioni M, Kumar S, Garbitt VM, Sharik ME, Henderson KJ, Tonon G, Tomura M, Miwa Y, Esplugues E, Flavell RA, Huber S, Canducci F, Rajkumar VS, Bergsagel PL, Bellone M. Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nature Communications 2018, 9: 4832. PMID: 30510245, PMCID: PMC6277390, DOI: 10.1038/s41467-018-07305-8.
- Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes developmentYu H, Gagliani N, Ishigame H, Huber S, Zhu S, Esplugues E, Herold KC, Wen L, Flavell RA. Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 10443-10448. PMID: 28894001, PMCID: PMC5625908, DOI: 10.1073/pnas.1705599114.
- TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestinePascual-Reguant A, Bayat Sarmadi J, Baumann C, Noster R, Cirera-Salinas D, Curato C, Pelczar P, Huber S, Zielinski CE, Löhning M, Hauser AE, Esplugues E. TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine. Mucosal Immunology 2017, 10: 1431-1442. PMID: 28198366, DOI: 10.1038/mi.2017.5.
- IL-10 Receptor Signaling Is Essential for TR1 Cell Function In VivoBrockmann L, Gagliani N, Steglich B, Giannou AD, Kempski J, Pelczar P, Geffken M, Mfarrej B, Huber F, Herkel J, Wan YY, Esplugues E, Battaglia M, Krebs CF, Flavell RA, Huber S. IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo. The Journal Of Immunology 2017, 198: 1130-1141. PMID: 28003377, PMCID: PMC5263184, DOI: 10.4049/jimmunol.1601045.
- Intestinal Tr1 cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development.Yu H , Gagliani N , Ishigame H , Huber S, Zhu S , Esplugues E , Herold KC , Wen L , Flavell RA. PNAS. 2017
- TFH cells progressively differentiate to regulate the germinal center responseWeinstein JS, Herman EI, Lainez B, Licona-Limón P, Esplugues E, Flavell R, Craft J. TFH cells progressively differentiate to regulate the germinal center response. Nature Immunology 2016, 17: 1197-1205. PMID: 27573866, PMCID: PMC5030190, DOI: 10.1038/ni.3554.
- Apoptosis in response to microbial infection induces autoreactive TH17 cellsCampisi L, Barbet G, Ding Y, Esplugues E, Flavell RA, Blander JM. Apoptosis in response to microbial infection induces autoreactive TH17 cells. Nature Immunology 2016, 17: 1084-1092. PMID: 27455420, PMCID: PMC5079524, DOI: 10.1038/ni.3512.
- Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammationPaterka M, Siffrin V, Voss JO, Werr J, Hoppmann N, Gollan R, Belikan P, Bruttger J, Birkenstock J, Jung S, Esplugues E, Yogev N, Flavell RA, Bopp T, Zipp F. Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammation. The EMBO Journal 2015, 35: 89-101. PMID: 26612827, PMCID: PMC4718005, DOI: 10.15252/embj.201591488.
- A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral ControlXin G, Schauder DM, Lainez B, Weinstein JS, Dai Z, Chen Y, Esplugues E, Wen R, Wang D, Parish IA, Zajac AJ, Craft J, Cui W. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control. Cell Reports 2015, 13: 1118-1124. PMID: 26527008, PMCID: PMC4859432, DOI: 10.1016/j.celrep.2015.09.069.
- Progressive differentiation of follicular B helper T cells regulates the germinal center response (IRC11P.430)Herman E, Weinstein J, Lainez B, Licona-Limón P, Esplugues E, Flavell R, Craft J. Progressive differentiation of follicular B helper T cells regulates the germinal center response (IRC11P.430). The Journal Of Immunology 2015, 194: 197.12-197.12. DOI: 10.4049/jimmunol.194.supp.197.12.
- Th17 cells transdifferentiate into regulatory T cells during resolution of inflammationGagliani N, Vesely M, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limón P, Paiva RS, Ching T, Weaver C, Zi X, Pan X, Fan R, Garmire LX, Cotton MJ, Drier Y, Bernstein B, Geginat J, Stockinger B, Esplugues E, Huber S, Flavell RA. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 2015, 523: 221-225. PMID: 25924064, PMCID: PMC4498984, DOI: 10.1038/nature14452.
- Dynamic signaling by T follicular helper cells during germinal center B cell selectionShulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft JE, Nussenzweig MC. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science 2014, 345: 1058-1062. PMID: 25170154, PMCID: PMC4519234, DOI: 10.1126/science.1257861.
- The Role of TH17-Associated Cytokines in Health and DiseaseO’Connor W, Esplugues E, Huber S. The Role of TH17-Associated Cytokines in Health and Disease. Journal Of Immunology Research 2014, 2014: 936270. PMID: 24872959, PMCID: PMC4020370, DOI: 10.1155/2014/936270.
- Oct-1 Regulates IL-17 Expression by Directing Interchromosomal Associations in Conjunction with CTCF in T CellsKim LK, Esplugues E, Zorca CE, Parisi F, Kluger Y, Kim TH, Galjart NJ, Flavell RA. Oct-1 Regulates IL-17 Expression by Directing Interchromosomal Associations in Conjunction with CTCF in T Cells. Molecular Cell 2014, 54: 56-66. PMID: 24613343, PMCID: PMC4058095, DOI: 10.1016/j.molcel.2014.02.004.
- Bcl6 expression specifies the T follicular helper cell program in vivoLiu X, Yan X, Zhong B, Nurieva RI, Wang A, Wang X, Martin-Orozco N, Wang Y, Chang SH, Esplugues E, Flavell RA, Tian Q, Dong C. Bcl6 expression specifies the T follicular helper cell program in vivo. Journal Of Experimental Medicine 2012, 209: 1841-1852. PMID: 22987803, PMCID: PMC3457730, DOI: 10.1084/jem.20120219.
- Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 DiabetesCzyzyk J, Henegariu O, Preston-Hurlburt P, Baldzizhar R, Fedorchuk C, Esplugues E, Bottomly K, Gorus FK, Herold K, Flavell RA. Enhanced Anti-Serpin Antibody Activity Inhibits Autoimmune Inflammation in Type 1 Diabetes. The Journal Of Immunology 2012, 188: 6319-6327. PMID: 22593614, PMCID: PMC3370061, DOI: 10.4049/jimmunol.1200467.
- Effector CD4+ T Cell Expression Signatures and Immune-Mediated Disease Associated GenesZhang W, Ferguson J, Ng SM, Hui K, Goh G, Lin A, Esplugues E, Flavell RA, Abraham C, Zhao H, Cho JH. Effector CD4+ T Cell Expression Signatures and Immune-Mediated Disease Associated Genes. PLOS ONE 2012, 7: e38510. PMID: 22715389, PMCID: PMC3371029, DOI: 10.1371/journal.pone.0038510.
- Mir-33 regulates cell proliferation and cell cycle progressionCirera-Salinas D, Pauta M, Allen RM, Salerno AG, Ramírez CM, Chamorro-Jorganes A, Wanschel AC, Lasuncion MA, Morales-Ruiz M, Suarez Y, Baldan A, Esplugues E, Fernández-Hernando C. Mir-33 regulates cell proliferation and cell cycle progression. Cell Cycle 2012, 11: 922-933. PMID: 22333591, PMCID: PMC3323796, DOI: 10.4161/cc.11.5.19421.
- Development of Autoimmune Diabetes in the Absence of Detectable IL-17A in a CD8-Driven Virally Induced ModelVan Belle TL, Esplugues E, Liao J, Juntti T, Flavell RA, von Herrath MG. Development of Autoimmune Diabetes in the Absence of Detectable IL-17A in a CD8-Driven Virally Induced Model. The Journal Of Immunology 2011, 187: 2915-2922. PMID: 21832162, PMCID: PMC3169711, DOI: 10.4049/jimmunol.1000180.
- Control of TH17 cells occurs in the small intestineEsplugues E, Huber S, Gagliani N, Hauser AE, Town T, Wan YY, O’Connor W, Rongvaux A, Van Rooijen N, Haberman AM, Iwakura Y, Kuchroo VK, Kolls JK, Bluestone JA, Herold KC, Flavell RA. Control of TH17 cells occurs in the small intestine. Nature 2011, 475: 514-518. PMID: 21765430, PMCID: PMC3148838, DOI: 10.1038/nature10228.
- miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signalingDávalos A, Goedeke L, Smibert P, Ramírez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suárez Y, Lai EC, Fernández-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 9232-9237. PMID: 21576456, PMCID: PMC3107310, DOI: 10.1073/pnas.1102281108.
- TGF-beta and TH17 CellsHuber S, Esplugues E, Flavell R. TGF-beta and TH17 Cells. 2011, 41-45. DOI: 10.1007/978-1-4419-9371-7_3.
- Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3− and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent MannerHuber S, Gagliani N, Esplugues E, O'Connor W, Huber FJ, Chaudhry A, Kamanaka M, Kobayashi Y, Booth CJ, Rudensky AY, Roncarolo MG, Battaglia M, Flavell RA. Th17 Cells Express Interleukin-10 Receptor and Are Controlled by Foxp3− and Foxp3+ Regulatory CD4+ T Cells in an Interleukin-10-Dependent Manner. Immunity 2011, 34: 554-565. PMID: 21511184, PMCID: PMC3113617, DOI: 10.1016/j.immuni.2011.01.020.
- CD69 limits early inflammatory diseases associated with immune response to Listeria monocytogenes infectionVega‐Ramos J, Alari‐Pahissa E, del Valle J, Carrasco‐Marín E, Esplugues E, Borràs M, Martínez‐A C, Lauzurica P. CD69 limits early inflammatory diseases associated with immune response to Listeria monocytogenes infection. Immunology And Cell Biology 2010, 88: 707-715. PMID: 20440294, DOI: 10.1038/icb.2010.62.
- Interleukin-17A is not Produced by T Cells During Anti-viral Immunity and Autoimmunity in a Model of Virus-induced Autoimmune DiabetesVan Belle T, Esplugues E, Liao J, Juntti T, Flavell R, von Herrath M. Interleukin-17A is not Produced by T Cells During Anti-viral Immunity and Autoimmunity in a Model of Virus-induced Autoimmune Diabetes. Clinical Immunology 2010, 135: s140. DOI: 10.1016/j.clim.2010.03.424.
- CD69 targeting differentially affects the course of collagen‐induced arthritisSancho D, Gómez M, del Hoyo G, Lamana A, Esplugues E, Lauzurica P, Martinez‐A C, Sánchez‐Madrid F. CD69 targeting differentially affects the course of collagen‐induced arthritis. Journal Of Leukocyte Biology 2006, 80: 1233-1241. PMID: 16921025, DOI: 10.1189/jlb.1205749.
- The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell KillingSaborit-Villarroya I, Del Valle J, Romero X, Esplugues E, Lauzurica P, Engel P, Martín M. The Adaptor Protein 3BP2 Binds Human CD244 and Links this Receptor to Vav Signaling, ERK Activation, and NK Cell Killing. The Journal Of Immunology 2005, 175: 4226-4235. PMID: 16177062, DOI: 10.4049/jimmunol.175.7.4226.
- Induction of tumor NK-cell immunity by anti-CD69 antibody therapyEsplugues E, Vega-Ramos J, Cartoixà D, Vazquez BN, Salaet I, Engel P, Lauzurica P. Induction of tumor NK-cell immunity by anti-CD69 antibody therapy. Blood 2005, 105: 4399-4406. PMID: 15692061, DOI: 10.1182/blood-2004-10-3854.
- Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2Lainez B, Fernandez-Real J, Romero X, Esplugues E, Cañete J, Ricart W, Engel P. Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2. International Immunology 2004, 16: 169-177. PMID: 14688072, DOI: 10.1093/intimm/dxh014.
- CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritisSancho D, Gómez M, Viedma F, Esplugues E, Gordón-Alonso M, García-López MA, de la Fuente H, Martínez-A C, Lauzurica P, Sánchez-Madrid F. CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis. Journal Of Clinical Investigation 2003, 112: 872-882. PMID: 12975472, PMCID: PMC193672, DOI: 10.1172/jci19112.
- Enhanced Antitumor Immunity in Mice Deficient in CD69Esplugues E, Sancho D, Vega-Ramos J, Martínez-A C, Syrbe U, Hamann A, Engel P, Sánchez-Madrid F, Lauzurica P. Enhanced Antitumor Immunity in Mice Deficient in CD69. Journal Of Experimental Medicine 2003, 197: 1093-1106. PMID: 12732655, PMCID: PMC2193974, DOI: 10.1084/jem.20021337.
- CD84 Functions as a Homophilic Adhesion Molecule and Enhances IFN-γ Secretion: Adhesion Is Mediated by Ig-Like Domain 1Martin M, Romero X, de la Fuente M, Tovar V, Zapater N, Esplugues E, Pizcueta P, Bosch J, Engel P. CD84 Functions as a Homophilic Adhesion Molecule and Enhances IFN-γ Secretion: Adhesion Is Mediated by Ig-Like Domain 1. The Journal Of Immunology 2001, 167: 3668-3676. PMID: 11564780, DOI: 10.4049/jimmunol.167.7.3668.