Luís Graça Lab

Lymphocyte Regulation

The Cellular Immunology Lab studies mechanisms able to induce and maintain immune tolerance. We study diseases, or animal models of human pathologies, where the immune system has an inappropriate action, such as in autoimmunity, transplantation or allergy.

We aim to reprogram the immune system, inducing the expansion of regulatory T cells capable of reinstating the tolerance state. We always strive to validate our experimental results in collaboration with clinical scientists.

Research Team

Research Areas

• Tolerance
• Regulatory T cells
• Autoimmunity
• Allergy
• Transplantation
• Monoclonal antibodies
• Animal models

Ongoing Research Projects

2015/2019 Informatics and Genomics of Helper T cells (ENLIGHT-TEN-MSCA-ITN-2015-675395 - H2020)

2015/2018 Multidisciplinary Strategy to Develop Novel Multicomponent Nanoscale Systems for Immune Modulation (UTAP-ICDT/DTP-FTO/0016/2014)

2015/2017 Regulação das respostas dos centros germinativos em doentes alérgicos (HMSP-ICT/0034/2013)

Awards

• Professor Jorge Silva Horta (second prize), 2019.
• Carregosa Bank - Ordem dos Médicos (honorable mention), 2018.
• iMM Innovators, TwinToInfect, 2017.
• NEDAI Prize in Autoimmunity Research, 2011.
• Young Entrepreneur Award 2010, from ANJE, 2010.
• Honorary mention in the ISCTE-IUL MIT-Portugal Venture Competition, 2010.
• BES National Innovation Award for Health Technologies, 2010.
• Idea to Product (I2P) Global Competition 2009, 2nd place, University of Texas at Austin, 2009.
• Prof. Heimburger Award in Coagulation Diseases, CSL Behring, 2009.

Selected Publications

• Fonseca VR, Romão VC, Água-Doce A, et al.(2018) Blood Tfr / Tfh ratio marks ectopic lymphoid structure formation and activated Tfh cells indicate disease activity in primary Sjögren’s syndrome. Arthritis & Rheumatology. 70: 774-784.
• Agua-Doce A, Caridade M, Oliveira VG,Bergman L, Lafaille MC, Lafaille JJ, Demengeot J,Graca L (2018) Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance, The Journal of Immunology. 200 (1) 101-109
• Maceiras AR, Fonseca VR, Agua-Doce A, Graca L.(2017) T follicular regulatory cells in mice and men. Immunology. 152(1):25-35.Review.
• Maceiras AR, Almeida SCP, Mariotti-Ferrandiz E, Chaara W, Jebbawi F, Six A,Hori S, Klatzmann D, Faro J, Graca L.(2017) T follicular helper and T follicular regulatory cells have different TCR specificity. Nat Commun. 21;8:15067.
• Maceiras AR, Graca L. (2015) Identification of Foxp3⁺ T follicular regulatory (Tfr)cells by flow cytometry. Methods Mol Biol. 1291:143-50
• Monteiro M, Agua-Doce A, Almeida CF, Fonseca-Pereira D, Veiga-Fernandes H,  Graca L (2015) IL-9 expression by invariante NKT cells is not imprinted during thymic development. J Immunol. 195(7):3463-3471
• Monteiro M, Graca L. (2014) iNKT cells: innate lymphocytes with a diverse response. Crit Rev Immunol. 34(1):81-90. Review.
• Oliveira VG, Agua-Doce A, Curotto de Lafaille M, Lafaille JJ, Graca L. (2013) Adjuvant facilitates anti-CD4 mediated immune tolerance to recombinant factor VIII in hemophilia through a Foxp3-independent mechanism that relies on IL-10. Blood. 121:3938-3945
• Monteiro M, Almeida CF, Agua-Doce A, Graca L. (2013) Induced IL-17-producing invariant Natural Killer T cells require activation in presence of TGF-β. J Immunol. 190:805-811
• Duarte J, Carrié N, Oliveira VG, Almeida C, Agua-Doce A, Rodrigues L, Simas P, Mars LT, Graca L. (2012) T cell apoptosis and induction of Foxp3+ regulatory T cells underlie the therapeutic efficacy of CD4-blockade in experimental autoimmune encephalomyelitis. J Immunol. 189:1680-1688.
• Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira V, Faro J, Graça L. (2011) Regulation of germinal centre reaction by Foxp3+ follicular regulatory T cells. J Immunol. 187: 4553-4560.
• Curotto de Lafaille MA, Lafaille JJ, Graca L. (2010) Mechanisms of tolerance and allergic sensitization in the airways and the lungs. Curr Opin Immunol. 22: 616-622.
• Monteiro M, Almeida CF, Caridade M, Ribot JC, Duarte J, Agua-Doce A, Wollenberg I, Silva-Santos B, Graça L. (2010) Identification of Regulatory Foxp3+ Invariant NKT Cells Induced by TGF-β. J Immunol. 185: 2157-2163.
• Duarte J, Agua-Doce A, Fonseca JE, Graça L. (2010) Modulation of synovial IL-17 and Foxp3 expression in the prevention of autoimmune arthritis. PLoS ONE. 5: e10558.
• Graça L, Le Moine A, Lin C-Y, Fairchild PJ, Cobbold SP, Waldmann H. (2004) Donor-specific transplantation tolerance: the paradoxial behavior of CD4+CD25+ T cells. Proceedings of the National Academy of Sciences USA 101: 10122-10126.
• Graça, L.*, Lin, C.-Y.*, Cobbold, S.P., Waldmann, H. (2002) Dominant transplantation tolerance impairs CD8+ T cell function but not expansion. Nature Immunology, 3: 1208-1213. (* Joint first authors)
• Graça, L., Cobbold, S.P., Waldmann, H. (2002) Identification of regulatory T cells in tolerated allografts. Journal of Experimental Medicine, 195: 1641-1646.

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