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Veldhoen, Marc
Lab

Regulação do Sistema Imunitário

Os tecidos epiteliais como a pele, o sistema respiratório e o sistema gastrontestinal funcionam como uma barreira entre o nosso organismo e os fatores externos. Estes tecidos para além de formarem uma barreira física que impede a passagem de agentes invasores, também incluem diversas células do sistema imunitário, que constituem a primeira linha de defesa contra microorganismos patogénicos.

A investigação que desenvolvemos pretende estudar a função das células do sistema imuntário na iniciação, modulação e resolução da resposta imune nos tecidos epiteliais, bem como na regulação da homeostase das células epiteliais. Este estudo pretende esclarecer os mecanismos que controlam a manutenção, ativação e função das células do sistema imunitário localizadas nas mucosas ou que se acumulam nestes tecidos. Deste modo, o objetivo do nosso laboratório é contribuir para a prevenção de respostas imunes indesejadas que podem resultar em infecções crónicas, alergias, doenças auto-imunes e risco aumentado de cancro.

  • Áreas de Investigação

    • Interações entre células imunes e células epiteliais
    • Homeostase tecidular
    • Diferenciação de células T helper
    • Influência dos fatores ambentais na imunidade
    • Imunologia das mucosas
  • Equipa de Investigação

    • Projectos de Investigação em Curso

      2014/2017 Engineering a multi-cell lineage multi-organism intestine (NC3R, UK)
      2015/2019 European Network Linking Informatics and Genomics of Helper T cells ENLIGHT-TEN ITN (H2020, EU)
      2016/2021 ERA Chair project (H2020, EU)

    • Prémios

      2011 EMBO Young Investigator programme

      2010 ERC starting grant

    • Publicações Seleccionadas

      • Brucklacher-Waldert V, Ferreira C, Stebegg M, Fesneau O, Innocentin S, Marie JC, Veldhoen M. (2017). Cellular Stress in the Context of an Inflammatory Environment Supports TGF-β-Independent T Helper-17 Differentiation. Cell Rep.
      • Veldhoen M. (2017). Interleukin 17 is a chief orchestrator of immunity. Nature Immunology.
      • Stubbs TM, Bonder MJ, Stark AK, Krueger F; BI Ageing Clock Team, von Meyenn F, Stegle O, Reik W. (2017). Multi-tissue DNA methylation age predictor in mouse. Genome Biology.
      • Goverse G, Molenaar R, Macia L, Tan J, Erkelens MN, Konijn T, Knippenberg M, Cook EC, Hanekamp D, Veldhoen M, Hartog A, Roeselers G, Mackay CR, Mebius RE. (2017). Diet-Derived Short Chain Fatty Acids Stimulate Intestinal Epithelial Cells To Induce Mucosal Tolerogenic Dendritic Cells. The Journal Immunology.
      • Veldhoen M. (2017). Th17 Cells Require You to Chew before You Swallow. Immunity.
      • Brucklacher-Waldert, V., Ferreira, C., Innocentin, S., Kamdar, S., Withers, D.R., Kullberg, C.M., and Veldhoen, M. (2016). Tbet or continued RORγt expression are not required for Th17-associated immunopathology. Journal of Immunology.
      • Barros-Martins, J., Schmolka, N., Fontinha, D., Pires de Miranda, M., Simas, J.P., Brok, I., Ferreira, C., Veldhoen, M., Silva-Santos, B., and Serre, K. (2016). Effector gammadelta T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors. Journal of Immunology.
      • Withers, D.R., Hepworth, M.R., Wang, X., Mackley, E.C., Halford, E.E., Dutton, E.E., Marriott, C.L., Brucklacher-Waldert, V., Veldhoen, M., Kelsen, J., et al. (2016). Transient inhibition of ROR-gammat therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. Nature Medicine 22, 319-323.
      • Bénézech, C., N-T. Luu, J.A. Walker, A.A Kruglov, Y. Loo, K. Nakamura, Y. Zhang, S. Nayar, L.H. Jones, A. Flores-Lanarica, A. McIntosh, J. Marshall, F. Barone, G. Besra, K. Miles, J.E. Allen, M. Gray, G. Kollias, A.F. Cunningham, D. Withers, K.M. Toellner, N.D. Jones, M. Veldhoen, S.A. Nedospasov, A.N.J. McKenzie and J.H. Caamaño. (2015) Inflammation-Induced Formation of Fat-Associated Lymphoid Clusters. Nature Immunology 16, 819-828.
      • Puccetti, P. , F. Fallarino, A. Italiano, I. Soubeyran, G. MacGrogan, M. Debled, V. Velasco, D. Bodet, S. Eimer, M. Veldhoen, G.C. Prendergast, M. Platten, A. Bessede and G. Guillemin. (2015) Accumulation of an Endogenous Tryptophan-Derived Metabolite in Colorectal and Breast Cancers. PLOS one 10, e0122046.
      • Stranks, A. J., A. L. Hansen, I. Panse, M. Mortensen, D. J. Ferguson, D. J. Puleston, K. Shenderov, A. S. Watson, M. Veldhoen, K. Phadwal, V. Cerundolo and A. K. Simon. (2015) Autophagy Controls Acquisition of Aging Features in Macrophages. Journal of Innate Immunology 7, no. 4 (2015): 375-391.
      • Linterman, M.A., Denton, A.E., Divekar, D.P., Zvetkova, I., Kane, L., Ferreira, C., Veldhoen, M., Clare, S., Dougan, G., Espeli, M., et al. (2014). CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection. Elife 3.
      • Marriott, C.L., Mackley, E.C., Ferreira, C., Veldhoen, M., Yagita, H., and Withers, D.R. (2014). OX40 controls effector CD4(+) T-cell expansion, not follicular T helper cell generation in acute Listeria infection. European Journal of Immunology 44, 2437-2447.
      • Zaid, A., Mackay, L.K., Rahimpour, A., Braun, A., Veldhoen, M., Carbone, F.R., Manton, J.H., Heath, W.R., and Mueller, S.N. (2014). Persistence of skin-resident memory T cells within an epidermal niche. Proceedings of the National Academy of Sciences of the United States of America 111, 5307-5312.
      • Sriskantharajah, S., Guckel, E., Tsakiri, N., Kierdorf, K., Brender, C., Ben-Addi, A., Veldhoen, M., Tsichlis, P.N., Stockinger, B., O'Garra, A., et al. (2014). Regulation of experimental autoimmune encephalomyelitis by TPL-2 kinase. Journal of Immunology 192, 3518-3529.
      • Mastelic, B., Freitas do Rosario, A.P., Veldhoen, M., Renauld, J.-C., Jarra, W., Sponaas, A.-M., Roetynck, S., Stockinger, B., and Langhorne, J. (2012). IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection. Frontiers in Immunology 3.
      • Li, Y., Innocentin, S., Withers, D.R., Roberts, N.A., Gallagher, A.R., Grigorieva, E.F., Wilhelm, C., and Veldhoen, M. (2011). Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation. Cell 147, 629-640.
      • Hirota, K., Duarte, J.H., Veldhoen, M., Hornsby, E., Li, Y., Cua, D.J., Ahlfors, H., Wilhelm, C., Tolaini, M., Menzel, U., et al. (2011). Fate mapping of IL-17-producing T cells in inflammatory responses. Nature Immunology 12, 255-263.
      • Teixeira-Coelho, M., Cruz, A., Carmona, J., Sousa, C., Ramos-Pereira, D., Saraiva, A.L., Veldhoen, M., Pedrosa, J., Castro, A.G., and Saraiva, M. (2011). TLR2 deficiency by compromising p19 (IL-23) expression limits Th 17 cell responses to Mycobacterium tuberculosis. International Immunology 23, 89-96
      • Martin, B., Hirota, K., Cua, D.J., Stockinger, B., and Veldhoen, M. (2009). Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity 31, 321-330.
      • Saraiva, M., Christensen, J.R., Veldhoen, M., Murphy, T.L., Murphy, K.M., and O'Garra, A. (2009). Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31, 209-219.
      • Bending, D., De La Pena, H., Veldhoen, M., Phillips, J.M., Uyttenhove, C., Stockinger, B., and Cooke, A. (2009). Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest 119, 565–572.
      • Veldhoen, M., Hirota, K., Christensen, J., O'Garra, A., and Stockinger, B. (2009). Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. The Journal of experimental medicine 206, 43-49.
      • Veldhoen, M., Uyttenhove, C., van Snick, J., Helmby, H., Westendorf, A., Buer, J., Martin, B., Wilhelm, C., and Stockinger, B. (2008). Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nature immunology 9, 1341-1346.
      • Veldhoen, M., Hirota, K., Westendorf, A.M., Buer, J., Dumoutier, L., Renauld, J.C., and Stockinger, B. (2008). The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106-109.
      • Veldhoen, M., Hocking, R.J., Flavell, R.A., and Stockinger, B. (2006). Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nature immunology 7, 1151-1156.
      • Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M., and Stockinger, B. (2006). TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189.
      • Veldhoen, M., Moncrieffe, H., Hocking, R.J., Atkins, C.J., and Stockinger, B. (2006). Modulation of dendritic cell function by naive and regulatory CD4+ T cells. J Immunol 176, 6202-6210.

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