Regulação de Linfócitos
O laboratório de investigação em Imunologia Celular estuda mecanismos de indução e manutenção de tolerância imunitária. Estudamos doenças, ou modelos animais de doenças, em que o sistema imunitário tem uma acção inapropriada, tais como autoimunidade, transplantação ou alergia.
Procuramos reprogramar o sistema imunitário, induzindo a expansão de células T reguladoras capazes de restabelecer o estado de tolerância. Tentamos sempre que possível validar os nossos resultados experimentais em colaboração com cientistas clínicos.
Equipa de Investigação
Áreas de Investigação
- Tolerância
- Linfócitos T reguladores
- Autoimunidade
- Alergia
- Transplantação
- Anticorpos monoclonais
- Modelos animais
Projetos de Investigação em Curso
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)
Prémios
- 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.
Publicações Selecionadas
- Deng J, Wei Y, Fonseca VR, Graca L*, Yu D* (2019) “Follicular helper and follicular regulatory T cells in autoimmune rheumatic diseases: phenotype, pathogenesis and targeted immunotherapies”. Nature Rev Rheumatol. In press. (* joint senior/corresponding authors)
- Fonseca VR, Romão VC, Agua-Doce A, Santos M, López-Presa D, Ferreiras AC, Fonseca JE, Graca L (2018) “The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome”. Arthritis Rheumatol. 70:774-784.
- Fonseca VR, Agua-Doce A, Maceiras AR, Pierson W, Ribeiro F, Romão VC, Pires AR, Silva SL, Fonseca JE, Sousa AE, Linterman MA, Graca L (2017) Human blood CXCR5+Foxp3+ T cells are indicators of ongoing humoral activity not fully licensed with suppressive function. Science Immunol. 2, eaan1487.
- Maceiras R, 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 from the same germinal centers have different TCR-specificity. Nature Commun. 8:15067.
- 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: 3463-3471.
- 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, Graca L. (2011) Regulation of germinal centre reaction by Foxp3+ follicular regulatory T cells. J Immunol 187: 4553-4560. (380 citations – report on the discovery of Tfr cells)
- Oliveira VG, Paiva R, Demengeot J, Graca L. (2011) Sub-optimal CD4 T cell activation triggers TGF-β-dependent conversion to Foxp3+ regulatory T cells Eur J Immunol 41:1249-55.