Geginat Jens

Principal Investigator

 

Bio

Jens Geginat graduated in Biochemistry at the Free University of Berlin, and obtained his PhD in 1999 at the Scientific Institute S. Raffaele DiBit in Milan in the lab of Ruggero Pardi. He then joined the Basel Institute for Immunology (BII) and worked with Antonio Lanzavecchia, from 2000 at the Research Institute for Biomedicine (IRB) in Bellinzona, Switzerland. In 2006 he was selected for a Junior Group Leader in Berlin of the University Hospital Charité at the German Rheumatology Research Centre (DRFZ) headed by Andreas Radbruch. In 2010 the Charité conferred him the Habilitation to teach Immunology at Universities. Since October 2009 he is leading the Autoimmunity Program at INGM. His main research interest is human T cell biology, in particular the characterization of regulatory and memory T-cell subsets. He has done relevant contributions to the understanding of how T-cell memory is generated and maintained. Moreover, his group was recently the first to identify human IL-10 producing regulatory T-cell subsets directly in vivo. The further characterization of these cells will clarify their role in immune-mediated human pathologies, and improve protocols for adoptive T cell therapy.

Publications

Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets.
Geginat J, Nizzoli G, Paroni M, Maglie S, Larghi P, Pascolo S, Abrignani S.
Front Immunol. 2015 Oct 13;6:527. doi: 10.3389/fimmu.2015.00527. eCollection 2015. Review.

Signal Strength and Metabolic Requirements Control Cytokine-Induced Th17 Differentiation of Uncommitted Human T Cells
Kastirr I, Crosti MC, Maglie S, Paroni M, Steckel B, Moro M, Pagani M, Abrignani S, Geginat J
Journal of Immunology. Sept 2015

IL-10-producing forkhead box protein 3-negative regulatory T cells inhibit B-cell responses and are involved in systemic lupus erythematosus.
Facciotti F, Gagliani N, Häringer B, Alfen JS, Penatti A, Maglie S, Paroni M, Iseppon A, Moro M, Crosti MC, Stölzel K, Romagnani C, Moroni G,Ingegnoli F, Torretta S, Pignataro L, Annoni A, Russo F, Pagani M, Abrignani S, Meroni P, Flavell R, Geginat J.
J Allergy Clin Immunol. 2015 Aug 25. pii: S0091-6749(15)00999-9. doi: 10.1016/j.jaci.2015.06.044. [Epub ahead of print]

Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation.
Gagliani N, Vesely MC, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limón P, Paiva R, 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 Apr 29. doi: 10.1038/nature14452. [Epub ahead of print]

The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4.
Ranzani V, Rossetti G, Panzeri I, Arrigoni A, Bonnal RJP, Curti S, Provasi E, Sugliano E, De Francesco R, Geginat J, Bodega B, Abrignani S, Pagani M.
Nat Immunol. 2015; 16: 318-25.

Plasticity of human CD4 T cell subsets.
Geginat J, Paroni M, Maglie S, Alfen JS, Kastirr I, Gruarin P, De Simone M, Pagani M, Abrignani S.
Front Immunol. 2014 Dec 16;5:630. doi: 10.3389/fimmu.2014.00630. eCollection 2014.

IL-21 Is a Central Memory T Cell-Associated Cytokine That Inhibits the Generation of Pathogenic Th1/17 Effector Cells.
Kastirr I, Maglie S, Paroni M, Alfen JS, Nizzoli G, Sugliano E, Crosti MC, Moro M, Steckel B, Steinfelder S, Stölzel K, Romagnani C, Botti F, Caprioli F, Pagani M, Abrignani S, Geginat J
J Immunol. 2014 Oct 1;193(7):3322-31.

Absence of a role for interleukin-13 in inflammatory bowel disease
Biancheri P, Di Sabatino A, Ammoscato F, Facciotti F, Caprioli F, Curciarello R, Hoque SS, Ghanbari A, Joe-Njoku I, Giuffrida P, Rovedatti L, Geginat J, Corazza GR, MacDonald TT.
Eur J Immunol. 2014 Feb;44(2):370-85. doi: 10.1002/eji.201343524.

Intracellular modulation, extracellular disposal and serum increase of MiR-150 mark lymphocyte activation
de Candia P, Torri A, Gorletta T, Fedeli M, Bulgheroni E, Cheroni C, Marabita F, Crosti M, Moro M, Pariani E, Romanò L, Esposito S, Mosca F, Rossetti G, Rossi RL, Geginat J, Casorati G, Dellabona P, Pagani M, Abrignani S.
PLoS One. 2013 Sep 26;8(9):e75348. doi: 10.1371/journal.pone.0075348. eCollection 2013.

The CD4-centered universe of human T cell subsets
Geginat J, Paroni M, Facciotti F, Gruarin P, Kastirr I, Caprioli F, Pagani M, Abrignani S.
Semin Immunol. 2013 Nov 15;25(4):252-62. doi: 10.1016/j.smim.2013.10.012. Epub 2013 Nov 1.

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses
Nizzoli G, Krietsch J, Weick A, Steinfelder S, Facciotti F, Gruarin P, Bianco A, Steckel B, Moro M, Crosti M, Romagnani C, Stölzel K, Torretta S, Pignataro L, Scheibenbogen C, Neddermann P, De Francesco R, Abrignani S, Geginat J.
Blood. 2013 Aug 8;122(6):932-42. doi: 10.1182/blood-2013-04-495424. Epub 2013 Jun 21.

Role of microRNAs and long-non-coding RNAs in CD4(+) T-cell differentiation
Pagani M, Rossetti G, Panzeri I, de Candia P, Bonnal RJ, Rossi RL, Geginat J, Abrignani S.
Immunol Rev. 2013 May;253(1):82-96. doi: 10.1111/imr.12055. Review.

Identification of new autoantigens by protein array indicates a role for IL4 neutralization in autoimmune hepatitis
Zingaretti C, Arigò M, Cardaci A, Moro M, Crosti M, Sinisi A, Sugliano E, Cheroni C, Marabita F, Nogarotto R, Bonnal RJ, Marcatili P, Marconi M, Zignego A, Muratori P, Invernizzi P, Colombatto P, Brunetto M, Bonino F, De Francesco R, Geginat J, Pagani M, Muratori L, Abrignani S, Bombaci M.
Mol Cell Proteomics. 2012 Dec;11(12):1885-97. doi: 10.1074/mcp.M112.018713. Epub 2012 Sep 20.

Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b.
R. L. Rossi, G. Rossetti, L. Wenandy, M. Moro, R. Sciarretta Birolo, R. J. P. Bonnal, S. Curti, S. Maglie, P. Gruarin, F. Marabita, D.Mascheroni, A.Ripamonti, M.Comelli, E. Trabucchi, R. De Francesco, J. Geginat, S. Abrignani and M. Pagani
Nature Immunolgy, 2011, 2011 June 26, 12, 796

Dual role of anti-TNF therapy: enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues
F. Bose, L. Raeli, C. Garutti, E. Frigerio, A. Cozzi, M. Crimi, F. Caprioli, R. Scavelli, G. Altomare, J. Geginat, S. Abrignani, and E. Real
Clinical Immunology,
2011 May;139(2):164-76

Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells
S. Steinfelder, S. Floess, U. Baron, L. Rivino, B. Häringer, B. Steckel, A. Gruetzkau, S. Olek, J. Geginat, J. Hühn, and A. Hamann  (equal contribution)
Blood,
2011, 117(10):2839-46

Biology of Interleukin-10
Robert Sabat, Gerald Grütz, Katarzyna Warszawska, Stefan Kirsch, Ellen Witte, Kerstin Wolk and Jens Geginat.
Cytokine and Growth Factor Reviews, 2010 Oct; 21(5):331-44

CCR6 is expressed on an IL-10 producing, auto-reactive memory T cell population with context-dependent regulatory function
L. Rivino, P. Gruarin, B. Häringer, S. Steinfelder, L. Lozza, E. Sugliano, A. Weick, D. Jarrossay, A. Kuehl, C. Loddenkemper, S. Abrignani, F. Sallusto, A. Lanzavecchia and J. Geginat
The Journal of Experimental Medicine, 2010, 207(3): 565-577

Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity
Na IK, Letsch A, Guerreiro M, Bauer S, Noack I, Geginat J, Reinke P, Loesch M, Kienapfel H, Thiel E, Volk HD, Scheibenbogen C.
J Immunotherapy, 2009 Nov-Dec;32(9):907-13

Identification and characterization of IL-10/IFN-g producing effector-like cells with regulatory function in human blood
B. Häringer, L. Lozza, B. Steckel, and J. Geginat
The Journal of Experimental Medicine, 2009 May 11;206(5):1009-17. Epub 2009 May 4

The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion and lineage commitment of primed human CD4+IL-7Rhi T cells
L. Lozza, L. Rivino, F G. Guarda, D. Jarossay, A. Rinaldi,. Bertoni, F. Sallusto, A. Lanzavecchia and J. Geginat
European Journal of Immunology, (Highlights) 2008 38(1): 30-39
accompanying commentary: V. Kalia, S. Sarkar and R. Ahmed: “Fine-tuning CD4+ central memory T cell heterogeneity by strength of stimulation”
European Journal of Immunology, (Highlights) 2008 38(1): 15-19

Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells
E. V. Acosta-Rodriguez, L. Rivino, J. Geginat, D. Jarrossay, M. Gattorno, A. Lanzavecchia, F. Sallusto and G. Napolitano
Nature Immunology, 2007, 8(6):639-646

Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA
B. Scheel, R. Teufel, J. Probst, J.-P. Carralot, J. Geginat, M. Radsak, D. Jarrossay, H. Wagner, G. Jung, H.-G. Rammensee, I. Hoerr and S. Pascolo
European Journal of Immunology, 2005, 35(5): 1557-66

Chemokine receptor expression identifies pre-Th1, pre-Th2 and non-polarized cells among human CD4+ central memory T cells
L. Rivino, M. Messi, D. Jarrossay, Antonio Lanzavecchia, Federica Sallusto and J. Geginat
The Journal of Experimental Medicine, 2004, 200 (6): 725-735

Central memory and effector memory T cell subsets: Function, generation and maintenance
F. Sallusto, J. Geginat, and A. Lanzavecchia
Annual Review of Immunology, 2004, 22: 745-763

T cell fitness determined by signal strength
A. Gett, F. Sallusto, A. Lanzavecchia and J. Geginat
Nature Immunology, 2003, 4:355-60
(Commentary: J. Bell: “Survival of the fittest” in Nat. Rev Immunol. 2003 3(4): 265)

Proliferation and differentiation potential of human CD8+ memory T cell subsets in response to antigen or homeostatic cytokines
J. Geginat, A. Lanzavecchia and F. Sallusto
Blood 2003, 101:4260-6

Cytokine-driven proliferation and differentiation of human naïve, central memory and effector memory CD4+ T cells
J. Geginat, F. Sallusto and A. Lanzavecchia
Pathologie Biologie, 2003, 51(2): 64-6

TCR-independent proliferation and differentiation of human CD4+ T cell subsets induced by cytokines
J. Geginat, S. Campagnaro, F. Sallusto, A. Lanzavecchia
Adv Exp Med Biol, 2002, 512:107-12

Functional  subsets of memory T cells identified by CCR7 expression
F. Sallusto, A. Langenkamp, J. Geginat and A. Lanzavecchia
Curr Top Microbiol Immunol, 2000, 251:167-71

CD28 and LFA-1 contribute to cyclosporin A-resistant T cell growth by stabilizing the IL-2 m-RNA through distinct signaling pathways
J. Geginat, B. Clissi, M. Moro, P. Dellabona, J. Bender and R. Pardi
European Journal of Immunology, 2000, 30: 1136-44

Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity
E. Bianchi, S. Denti, A. Granata, G. Bossi, J. Geginat, A. Villa, L. Rogge and R. Pardi
Nature, 2000, 404: 617-21

Chemokines fail to upregulate 1 integrin-dependent adhesion in human Th2 T lymphocytes
B. Clissi, D. d’Ambrosio, J. Geginat, L. Colantonio, A. Morrot, N. W. Freshney, J. Downward, F. Sinigaglia and R. Pardi
The Journal of Immunology, 2000, 164: 3292-300

8B4/20, a private CD43 epitope on developing human thymocytes, is involved in thymocyte maturation
M. Fabbi, J. Geginat, M. Tiso, D. Ramarli, D. Parent, A. Bargellesi-Severi and E. Remold -O’ Donnell
The Journal of Immunology, 1999, 163: 5964-70

Anchorage-dependence of mitogen-induced G1 to S transition in primary human T lymphocytes
J. Geginat, G. Bossi, J. R. Bender and R. Pardi
The Journal of Immunology, 1999, 162: 5085-93

INGM researches are supported by