Autoimmune Diseases; Immune System Diseases; Autoimmunity
Public Health Interests
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).
- 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. in press.
TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine.
Pascual-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. Mucosal immunology. 2017
TFH cells progressively differentiate to regulate the germinal center response.
Weinstein JS, Herman EI, Lainez B, Licona-Limón P, Esplugues E, Flavell R, Craft J. Nature immunology. 2016; 17(10):1197-1205.
Apoptosis in response to microbial infection induces autoreactive TH17 cells.
Campisi L, Barbet G, Ding Y, Esplugues E, Flavell RA, Blander JM. Nature immunology. 2016; 17(9):1084-92.
Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation.
Gagliani N, Amezcua Vesely MC, 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. Nature. 2015; 523(7559):221-5.
Dynamic signaling by T follicular helper cells during germinal center B cell selection.
Shulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft JE, Nussenzweig MC. Science. 2014; 345(6200):1058-62.
Development of autoimmune diabetes in the absence of detectable IL-17A in a CD8-driven virally induced model.
Van Belle TL*, Esplugues E*, Liao J, Juntti T, Flavell RA, von Herrath MG. Journal of immunology. 2011; 187(6):2915-22. (*first authors)
Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells.
Kim LK, Esplugues E, Zorca CE, Parisi F, Kluger Y, Kim TH, Galjart NJ, Flavell RA. Molecular cell. 2014; 54(1):56-66.
Bcl6 expression specifies the T follicular helper cell program in vivo.
Liu 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. The Journal of experimental medicine. 2012; 209(10):1841-52, S1-24.
Control of TH17 cells occurs in the small intestine.
Esplugues E*#, Huber S*, Gagliani N, Hauser AE, Town T, Wan YY, O'Connor W Jr, Rongvaux A, Van Rooijen N, Haberman AM, Iwakura Y, Kuchroo VK, Kolls JK, Bluestone JA, Herold KC, Flavell RA#. Nature. 2011; 475(7357):514-8 (*first authors, #corresponding authors)
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling.
Dávalos 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. PNAS. 2011; 108(22):9232-7.
Th17 cells express interleukin-10 receptor and are controlled by Foxp3⁻ and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner.
Huber S*, Gagliani N*, Esplugues E*, O'Connor W Jr, Huber FJ, Chaudhry A, Kamanaka M, Kobayashi Y, Booth CJ, Rudensky AY, Roncarolo MG, Battaglia M, Flavell RA. Immunity. 2011; 34(4):554-65. (*first authors)
Induction of tumor NK-cell immunity by anti-CD69 antibody therapy.
Esplugues E, Vega-Ramos J, Cartoixà D, Vazquez BN, Salaet I, Engel P, Lauzurica P. Blood. 2005; 105(11):4399-406.
CD69 downregulates autoimmune reactivity through active transforming growth factor-beta production in collagen-induced arthritis.
Sancho 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. The Journal of clinical investigation. 2003; 112(6):872-82.
Enhanced antitumor immunity in mice deficient in CD69.
Esplugues E, Sancho D, Vega-Ramos J, Martínez C, Syrbe U, Hamann A, Engel P, Sánchez-Madrid F, Lauzurica P. The Journal of experimental medicine. 2003; 197(9):1093-106.