{"id":1324,"date":"2024-07-31T14:30:21","date_gmt":"2024-07-31T14:30:21","guid":{"rendered":"https:\/\/gimm.pt\/our-work\/laboratories\/laboratorio-luis-graca\/"},"modified":"2026-04-16T11:46:41","modified_gmt":"2026-04-16T11:46:41","slug":"laboratorio-luis-graca","status":"publish","type":"lab","link":"https:\/\/gimm.pt\/pt-pt\/o-nosso-trabalho\/laboratorios\/laboratorio-luis-graca\/","title":{"rendered":"Laborat\u00f3rio Lu\u00eds Gra\u00e7a"},"content":{"rendered":"\n<h3 class=\"wp-block-heading\">Regula\u00e7\u00e3o dos linf\u00f3citos<\/h3>\n\n\n\n<p><\/p>\n\n\n\n<p>O nosso grupo estuda a forma como as respostas imunit\u00e1rias s\u00e3o reguladas. Dissecamos os mecanismos que mant\u00eam a homeostasia imunit\u00e1ria, permitindo uma prote\u00e7\u00e3o eficaz contra infe\u00e7\u00f5es sem desencadear inflama\u00e7\u00e3o nem danos tecidulares. Compreender como o equil\u00edbrio imunit\u00e1rio \u00e9 mantido permite desenvolver m\u00e9todos para alterar esse equil\u00edbrio de forma terap\u00eautica: reduzindo a imunidade quando o sistema imunit\u00e1rio est\u00e1 a causar danos, como na autoimunidade, na alergia e na rejei\u00e7\u00e3o de transplantes, ou potenciando a resposta imunit\u00e1ria para melhorar vacinas ou a a\u00e7\u00e3o contra infe\u00e7\u00f5es ou cancro.<\/p>\n\n\n\n<p>Estudamos linf\u00f3citos que regulam as respostas imunit\u00e1rias, como as c\u00e9lulas T reguladoras e as c\u00e9lulas T foliculares reguladoras. O nosso interesse centra-se na regula\u00e7\u00e3o das respostas dos centros germinativos, nas c\u00e9lulas T foliculares auxiliares e na produ\u00e7\u00e3o de anticorpos. M\u00e9todos de ponta em multi\u00f3mica de c\u00e9lula \u00fanica e espacial, bem como abordagens computacionais, s\u00e3o fundamentais para explorar a biologia de amostras cl\u00ednicas em contextos de sa\u00fade e doen\u00e7a.<\/p>\n\n\n\n<p>Num futuro pr\u00f3ximo, as estrat\u00e9gias terap\u00eauticas para modular o sistema imunit\u00e1rio ir\u00e3o melhorar a qualidade de vida das pessoas que sofrem de doen\u00e7as imunomediadas.<\/p>\n\n\n\n<p><\/p>\n\n\n<div style=\"position: relative;\" id=\"\" class=\"alignfull\">\n\n\t\n\t\n\t<div style=\"background-color: unset;\" class=\"wrapper_section  \">\n\n\t\t<section >\n\t\t\t<div class=\"container\">\n\n\n\t\t\t\t\t\t\t\t<div class=\"acf-innerblocks-container\">\n<div id=\"\" class=\"wp-block-gimm-partner-list\">\n\t<div class=\"row\">\n\t\t<div class=\"col-lg-12 wow fadeIn\">\n\t\t\t<h3 class=\"gimm_title pt-4 mb-2 wow fadeIn\">Financiamento<\/h3>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-carousel owl-theme owl-loaded owl-drag\">\n\t\t\t\t\t\t\t<div class=\"owl-stage-outer\">\n\t\t\t\t\t\t\t\t<div class=\"owl-stage\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-item \">\n\t\t\t\t\t\t\t\t\t\t\t<div class=\"item text-center\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" style=\"max-height:150px; object-fit: contain;\" class=\"img-fluid\" src=\"https:\/\/gimm.pt\/wp-content\/uploads\/2024\/11\/2022_FCT_Logo_A_horizontal_preto.png\"\n\t\t\t\t\t\t\t\t\t\t\t\t\t\talt=\"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-item \">\n\t\t\t\t\t\t\t\t\t\t\t<div class=\"item text-center\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" style=\"max-height:150px; object-fit: contain;\" class=\"img-fluid\" src=\"https:\/\/gimm.pt\/wp-content\/uploads\/2024\/07\/gimm_partners_fundacaolc-1.jpg\"\n\t\t\t\t\t\t\t\t\t\t\t\t\t\talt=\"&#8220;la caixa&#8221; Foundation\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-item \">\n\t\t\t\t\t\t\t\t\t\t\t<div class=\"item text-center\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" style=\"max-height:150px; object-fit: contain;\" class=\"img-fluid\" src=\"https:\/\/gimm.pt\/wp-content\/uploads\/2024\/12\/European_Commission_Logo.svg_.png\"\n\t\t\t\t\t\t\t\t\t\t\t\t\t\talt=\"Horizon EU\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-item \">\n\t\t\t\t\t\t\t\t\t\t\t<div class=\"item text-center\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" style=\"max-height:150px; object-fit: contain;\" class=\"img-fluid\" src=\"https:\/\/gimm.pt\/wp-content\/uploads\/2025\/03\/Logo_Merck_KGaA_2015.svg_.png\"\n\t\t\t\t\t\t\t\t\t\t\t\t\t\talt=\"Merck KGaA\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<div class=\"owl-item \">\n\t\t\t\t\t\t\t\t\t\t\t<div class=\"item text-center\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" style=\"max-height:150px; object-fit: contain;\" class=\"img-fluid\" src=\"https:\/\/gimm.pt\/wp-content\/uploads\/2025\/04\/msca.png\"\n\t\t\t\t\t\t\t\t\t\t\t\t\t\talt=\"Marie Sk\u0142odowska-Curie Actions\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"owl-nav disabled\"><button type=\"button\" role=\"presentation\" class=\"owl-prev\"><span aria-label=\"Previous\">\u2039<\/span><\/button><button type=\"button\" role=\"presentation\"\n\t\t\t\t\t\t\t\t\tclass=\"owl-next\"><span aria-label=\"Next\">\u203a<\/span><\/button><\/div>\n\t\t\t\t\t\t\t<div class=\"owl-dots disabled\"><button role=\"button\" class=\"owl-dot active\"><span><\/span><\/button><\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/section>\n\t<\/div>\n\n<\/div>\n\n<div style=\"position: relative;\" id=\"\" class=\"alignfull\">\n\n\t\n\t\n\t<div style=\"background-color: unset;\" class=\"wrapper_section divider  \">\n\n\t\t<section >\n\t\t\t<div class=\"container\">\n\n\n\t\t\t\t\t\t\t\t<div class=\"acf-innerblocks-container\">\n<div id=\"\" class=\"wp-block-gimm-accordion\">\n\n\t<div class=\"accordion\" id=\"accordion\">\n\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-areas-de-investigacao\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#areas-de-investigacao\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"areas-de-investigacao\">\n\t\t\t\t\t\t\t<h3>\u00c1reas de Investiga\u00e7\u00e3o<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"areas-de-investigacao\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<ul>\n<li style=\"font-weight: 400\">C\u00e9lulas T reguladoras e toler\u00e2ncia imunit\u00e1ria<\/li>\n<li style=\"font-weight: 400\">Biologia dos centros germinativos, c\u00e9lulas T foliculares auxiliares (Tfh) e c\u00e9lulas T foliculares reguladoras (Tfr) e regula\u00e7\u00e3o da produ\u00e7\u00e3o de anticorpos<\/li>\n<li style=\"font-weight: 400\">Investiga\u00e7\u00e3o Cl\u00ednica<\/li>\n<li style=\"font-weight: 400\">Autoimunidade<\/li>\n<li style=\"font-weight: 400\">Alergia<\/li>\n<li style=\"font-weight: 400\">Transplanta\u00e7\u00e3o<\/li>\n<li style=\"font-weight: 400\">Vacinas<\/li>\n<li style=\"font-weight: 400\">Infe\u00e7\u00e3o e Imunidade<\/li>\n<li style=\"font-weight: 400\">Biologia computacional e bioinform\u00e1tica<\/li>\n<li style=\"font-weight: 400\">Epidemiologia<\/li>\n<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-projetos\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#projetos\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"projetos\">\n\t\t\t\t\t\t\t<h3>Projetos<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"projetos\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<div>\n<p><strong>2024\/2027:<\/strong> ERC-Portugal: Finding the biological pathway connecting immune dysregulation and oncogenesis in Sjogren&#8217;s disease. Coordena\u00e7\u00e3o: Lu\u00eds Gra\u00e7a. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Lisboa, PT).<\/p>\n<\/div>\n<div>\n<p><strong>2023\/2026:<\/strong> Modulation of human antibody responses by T follicular helper subsets. Coordena\u00e7\u00e3o: Lu\u00eds Gra\u00e7a. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Lisboa, PT).<\/p>\n<\/div>\n<div>\n<p><strong>2024\/2025:<\/strong>Ending COVID-19 variants of concern through cohort studies (END-VOC). Coordena\u00e7\u00e3o de WP: Lu\u00eds Gra\u00e7a. Ag\u00eancia Financiadora: European Union, Horizon 101046314.<\/p>\n<\/div>\n<div>\n<p><strong>2024\/2025:<\/strong> Immu3Dorg-unveiling immune system dynamics in disease: exploiting 3D human organoids for drug testing. Coordena\u00e7\u00e3o: Diana Matias. Ag\u00eancia Financiadora: CTI-Centro de Tecnologia e Inova\u00e7\u00e3o IMM (Lisbon, PT).<\/p>\n<\/div>\n<div>\n<p><strong>2023\/2025:<\/strong> Reconstructing immune dysregulation leading to therapeutic resistance in Crohn\u2019s disease. Coordena\u00e7\u00e3o: Lu\u00eds Gra\u00e7a. Ag\u00eancia Financiadora: Merck Sharp and Dohme (Rahway, NJ, US).<\/p>\n<\/div>\n<div>\n<p><strong>2022\/2026:<\/strong> PolyMuTEs- Polymeric nanoparticles-based multivalent mABs against glioblastoma for T-cell engagement. Coordena\u00e7\u00e3o: Diana Matias. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o &#8220;la Caixa&#8221; (Barcelona, ES).<\/p>\n<\/div>\n<div>\n<p><strong>2022\/2025:<\/strong> Harnessing germinal centre regulation for improved vaccines. Coordena\u00e7\u00e3o: Lu\u00eds Gra\u00e7a. Ag\u00eancia Financiadora: Funda\u00e7\u00e3o &#8220;la Caixa&#8221; (Barcelona, ES).<\/p>\n<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-publicacoes-seleccionadas\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#publicacoes-seleccionadas\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"publicacoes-seleccionadas\">\n\t\t\t\t\t\t\t<h3>Publica\u00e7\u00f5es Seleccionadas<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"publicacoes-seleccionadas\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p class=\"\" data-start=\"95\" data-end=\"468\"><strong data-start=\"95\" data-end=\"303\">Kumar S, Basto AP, Ribeiro F, Almeida SCP, Campos P, Peres C, Pulvirenti N, Al-Khalidi S, Kilbey A, Tosello J, Piaggio E, Russo M, Gama-Carvalho M, Coffelt SB, Roberts EW, Geginat J, Florindo HF, Graca L.<\/strong> (2024) Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue. <em data-start=\"404\" data-end=\"418\">Cell Discov.<\/em> 10:64. <a class=\"cursor-pointer\" target=\"_new\" rel=\"noopener\" data-start=\"426\" data-end=\"468\">https:\/\/doi.org\/10.1038\/s41421-024-00681-0<\/a><\/p>\n<p data-start=\"95\" data-end=\"468\"><em>Nesta publica\u00e7\u00e3o utiliz\u00e1mos scRNAseq, transcript\u00f3mica espacial e algoritmos de aprendizagem autom\u00e1tica para caracterizar a biologia das c\u00e9lulas Tfh induzidas em resposta a respostas imunit\u00e1rias do tipo 1 e do tipo 2. Identific\u00e1mos uma popula\u00e7\u00e3o de c\u00e9lulas Tfh Gzmk+ induzida em respostas do tipo 1.<\/em><\/p>\n<p class=\"\" data-start=\"470\" data-end=\"679\"><strong data-start=\"470\" data-end=\"557\">Malato J, Ribeiro RM, Leite PP, Casaca P, Antunes C, Fonseca VR, Gomes MC, Graca L.<\/strong> (2023) Stability of hybrid versus vaccine immunity against BA.5 infection over 8 months. <em data-start=\"647\" data-end=\"667\">Lancet Infect Dis.<\/em> 23:148\u2013150.<\/p>\n<p data-start=\"470\" data-end=\"679\"><em>Calcul\u00e1mos o decl\u00ednio na taxa de prote\u00e7\u00e3o contra a infe\u00e7\u00e3o por SARS-CoV-2 (waning imunit\u00e1rio) ap\u00f3s imunidade h\u00edbrida, recorrendo a registos nacionais e modelos matem\u00e1ticos. Recebeu ampla cobertura medi\u00e1tica, incluindo um coment\u00e1rio na Nature, e influenciou o calend\u00e1rio de refor\u00e7os vacinais na UE (ver tamb\u00e9m Graca et al 2023. Nature Immunol. 10.1038\/s41590-034-01518-w).<\/em><\/p>\n<p class=\"\" data-start=\"681\" data-end=\"917\"><strong data-start=\"681\" data-end=\"781\">Malato J, Ribeiro RM, Leite PP, Casaca P, Fernandes E, Antunes C, Fonseca VR, Gomes MC, Graca L.<\/strong> (2022) Risk of BA.5 infection in individuals exposed to prior SARS-CoV-2 variants. <em data-start=\"865\" data-end=\"880\">N Engl J Med.<\/em><a class=\"cursor-pointer\" target=\"_new\" rel=\"noopener\" data-start=\"881\" data-end=\"917\">https:\/\/doi.org\/10.1056\/NEJMc2209479<\/a><\/p>\n<p data-start=\"681\" data-end=\"917\"><em>Nesta publica\u00e7\u00e3o, quantific\u00e1mos a prote\u00e7\u00e3o conferida pela infe\u00e7\u00e3o com Omicron BA.1 em indiv\u00edduos vacinados contra uma infe\u00e7\u00e3o subsequente com Omicron BA.5. A EMA utilizou esta informa\u00e7\u00e3o para fundamentar a decis\u00e3o de autorizar vacinas baseadas em BA.1 quando a subvariante BA.5 j\u00e1 era dominante. Teve um impacto medi\u00e1tico muito amplo (Altmetric: percentil 99%, 95% dentro do NEJM).<\/em><\/p>\n<p class=\"\" data-start=\"919\" data-end=\"1172\"><strong data-start=\"919\" data-end=\"1072\">Kumar S, Fonseca VR, Ribeiro F, Basto AP, Agua-Doce A, Monteiro M, Miragaia RJ, Gomes T, Piaggio E, Segura E, Gama-Carvalho M, Teichmann SA, Graca L.<\/strong> (2021) Developmental bifurcation of human T follicular regulatory cells. <em data-start=\"1146\" data-end=\"1160\">Sci Immunol.<\/em> 6:eabd8411.<\/p>\n<p data-start=\"919\" data-end=\"1172\"><em>O estudo da diferencia\u00e7\u00e3o das c\u00e9lulas Tfh e Tfr humanas era dif\u00edcil, uma vez que os sistemas experimentais in vitro (especialmente antes do estabelecimento dos organoides de am\u00edgdala) apresentavam limita\u00e7\u00f5es significativas. Super\u00e1mos este desafio analisando a diferencia\u00e7\u00e3o das c\u00e9lulas Tfh e Tfr in vivo atrav\u00e9s de scRNAseq e novos m\u00e9todos computacionais. Definimos a sequ\u00eancia de eventos moleculares que as c\u00e9lulas Tfh e Tfr percorrem durante a sua diferencia\u00e7\u00e3o no tecido linfoide secund\u00e1rio humano.<\/em><\/p>\n<p class=\"\" data-start=\"1174\" data-end=\"1434\"><strong data-start=\"1174\" data-end=\"1219\">Deng J, Wei Y, Fonseca VR, Graca L, Yu D.<\/strong> (2019) Follicular helper and follicular regulatory T cells in autoimmune rheumatic diseases: phenotype, pathogenesis and targeted immunotherapies. <em data-start=\"1367\" data-end=\"1387\">Nat Rev Rheumatol.<\/em> 15:475. (<em data-start=\"1397\" data-end=\"1433\">joint senior\/corresponding authors<\/em>)<\/p>\n<p data-start=\"1174\" data-end=\"1434\"><em>Revis\u00e3o escrita em colabora\u00e7\u00e3o com Di Yu (Melbourne), na qual discutimos de que forma as popula\u00e7\u00f5es de c\u00e9lulas Tfh e Tfr podem ser reguladores celulares-chave de doen\u00e7as reum\u00e1ticas autoimunes, incluindo a SSj.<\/em><\/p>\n<p class=\"\" data-start=\"1436\" data-end=\"1796\"><strong data-start=\"1436\" data-end=\"1534\">Fonseca VR, Rom\u00e3o VC, Agua-Doce A, Santos M, L\u00f3pez-Presa D, Ferreiras AC, Fonseca JE, Graca L.<\/strong> (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 Sj\u00f6gren&#8217;s Syndrome. <em data-start=\"1762\" data-end=\"1784\">Arthritis Rheumatol.<\/em> 70:774\u2013784.<\/p>\n<p data-start=\"1436\" data-end=\"1796\"><em>Esta publica\u00e7\u00e3o estabeleceu que subpopula\u00e7\u00f5es circulantes de Tfh e Tfr conseguem discriminar doentes com SSj com diferentes caracter\u00edsticas cl\u00ednicas. Entre elas, as c\u00e9lulas Tfh PD-1+ICOS+ no sangue perif\u00e9rico correlacionaram-se estreitamente com a atividade da doen\u00e7a. Este artigo foi destacado na Nat Rev Rheumatol e na Arthritis Rheumatol.<\/em><\/p>\n<p class=\"\" data-start=\"1798\" data-end=\"2092\"><strong data-start=\"1798\" data-end=\"1936\">Fonseca VR, Agua-Doce A, Maceiras AR, Pierson W, Ribeiro F, Rom\u00e3o VC, Pires AR, Silva SL, Fonseca JE, Sousa AE, Linterman MA, Graca L.<\/strong> (2017) Human blood CXCR5+Foxp3+ T cells are indicators of ongoing humoral activity not fully licensed with suppressive function. <em data-start=\"2066\" data-end=\"2080\">Sci Immunol.<\/em> 2:eaan1487.<\/p>\n<p data-start=\"1798\" data-end=\"2092\"><em>Publica\u00e7\u00e3o de refer\u00eancia que estabeleceu a biologia das c\u00e9lulas Tfr circulantes humanas e o seu papel na SSj. Envolveu o estudo de amostras cl\u00ednicas de doentes com SSj, am\u00edgdalas pedi\u00e1tricas com sangue emparelhado, uma coorte de profissionais de sa\u00fade vacinados contra a gripe e indiv\u00edduos com defici\u00eancia de BTK sem c\u00e9lulas B (para estabelecer rela\u00e7\u00f5es mecan\u00edsticas). Coment\u00e1rio na Nature Immunol.<\/em><\/p>\n<p class=\"\" data-start=\"2094\" data-end=\"2357\"><strong data-start=\"2094\" data-end=\"2210\">Maceiras R, Almeida SCP, Mariotti-Ferrandiz E, Chaara W, Jebbawi F, Six A, Hori S, Klatzmann D, Faro J, Graca L.<\/strong> (2017) T follicular helper and T follicular regulatory cells from the same germinal centers have different TCR-specificity. <em data-start=\"2335\" data-end=\"2348\">Nat Commun.<\/em> 8:15067.<\/p>\n<p data-start=\"2094\" data-end=\"2357\"><em>Publica\u00e7\u00e3o importante que estabeleceu que, dentro do mesmo centro germinativo, as c\u00e9lulas Tfh e Tfr possuem um repert\u00f3rio de TCR distinto: enquanto o TCR das c\u00e9lulas Tfh \u00e9 direcionado para o antig\u00e9nio imunizante, as c\u00e9lulas Tfr apresentam TCRs relacionados com o repert\u00f3rio das c\u00e9lulas Treg e direcionados para autoantig\u00e9nios. Este achado apoia uma divis\u00e3o de fun\u00e7\u00f5es: enquanto as c\u00e9lulas Tfh promovem o desenvolvimento de c\u00e9lulas B de alta afinidade, as c\u00e9lulas Tfr previnem o surgimento de autorreatividade. Mais recentemente, foram identificadas popula\u00e7\u00f5es adicionais de Tfr que se diferenciam a partir de Tfh (ver Graca et al 2023, Sci Immunol 8:eadg7526).<\/em><\/p>\n<p class=\"\" data-start=\"2359\" data-end=\"2599\"><strong data-start=\"2359\" data-end=\"2434\">Oliveira VG, Agua-Doce A, Curotto de Lafaille MA, Lafaille JJ, Graca L.<\/strong> (2013) Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice through a Foxp3-independent mechanism that relies on IL-10. <em data-start=\"2577\" data-end=\"2584\">Blood<\/em>121:3936\u20133945.<\/p>\n<p data-start=\"2359\" data-end=\"2599\"><em>Esta publica\u00e7\u00e3o levou \u00e0 perce\u00e7\u00e3o de que os adjuvantes s\u00e3o importantes para potenciar as respostas imunit\u00e1rias, mas podem tamb\u00e9m ser determinantes para recrutar mecanismos espec\u00edficos de toler\u00e2ncia imunit\u00e1ria. Influenciou investiga\u00e7\u00e3o subsequente (no meu grupo e noutros) sobre o impacto dos adjuvantes na polariza\u00e7\u00e3o de Tfh, Tfr e Treg e na regula\u00e7\u00e3o imunit\u00e1ria.<\/em><\/p>\n<p class=\"\" data-start=\"2601\" data-end=\"2804\"><strong data-start=\"2601\" data-end=\"2685\">Wollenberg I, Agua-Doce A, Hern\u00e1ndez A, Almeida C, Oliveira VG, Faro J, Graca L.<\/strong> (2011) Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. <em data-start=\"2777\" data-end=\"2789\">J Immunol.<\/em> 187:4553\u20134560.<\/p>\n<p data-start=\"2601\" data-end=\"2804\"><em>Esta publica\u00e7\u00e3o relata a descoberta das c\u00e9lulas Tfr como reguladores-chave da resposta dos centros germinativos, tendo influenciado a minha orienta\u00e7\u00e3o de investiga\u00e7\u00e3o desde ent\u00e3o.<\/em><\/p>\n<p>Uma lista completa de publica\u00e7\u00f5es pode ser encontrada <a href=\"https:\/\/scholar.google.co.uk\/citations?user=DUYZctUAAAAJ&amp;hl=pt-PT\">aqui<\/a>.<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-premios\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#premios\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"premios\">\n\t\t\t\t\t\t\t<h3>Pr\u00e9mios<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"premios\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<div>\n<p><strong><span lang=\"PT\">2023:<\/span><\/strong><span lang=\"PT\">\u00a0Pr\u00e9mio Pfizer em Investiga\u00e7\u00e3o Cl\u00ednica; Pfizer \/ Sociedade das Ci\u00eancias M\u00e9dicas de Lisboa.<\/span><\/p>\n<\/div>\n<div>\n<p><strong><span lang=\"PT\">2023:<\/span><\/strong><span lang=\"PT\">\u00a0Medalha de M\u00e9rito da Freguesia de Alvalade.<\/span><\/p>\n<\/div>\n<div>\n<p><strong><span lang=\"PT\">2019:<\/span><\/strong><span lang=\"PT\"> Research Excellence Award. Pr\u00e9mios Cient\u00edficos Caixa Geral de Dep\u00f3sitos\/Universidade de Lisboa.<\/span><\/p>\n<\/div>\n<div>\n<p><strong>2017:<\/strong>\u00a0iMM Innovators, TwinToInfect.<\/p>\n<\/div>\n<div>\n<p><strong>2011:<\/strong>\u00a0NEDAI Prize in Autoimmunity Research.<\/p>\n<\/div>\n<div>\n<p><strong>2010:<\/strong>\u00a0Young Entrepreneur Award 2010, National Society of Entrepreneurship (ANJE).<\/p>\n<\/div>\n<div>\n<p><strong>2010:<\/strong>\u00a0National Innovation Award for Health Technologies; Banco Espirito Santo (BES).<\/p>\n<\/div>\n<div>\n<p><strong>2009:<\/strong>\u00a0Prof. Heimburger Award in Coagulation Diseases, CSL Behring.<\/p>\n<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-contribuicoes-para-a-sociedade\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#contribuicoes-para-a-sociedade\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"contribuicoes-para-a-sociedade\">\n\t\t\t\t\t\t\t<h3>Contribui\u00e7\u00f5es para a Sociedade<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"contribuicoes-para-a-sociedade\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p style=\"font-weight: 400\">Lu\u00eds Gra\u00e7a preside ao Comit\u00e9 T\u00e9cnico Consultivo Nacional de Imuniza\u00e7\u00e3o para a vacina\u00e7\u00e3o sazonal contra a gripe e a COVID-19.<\/p>\n<h2 style=\"font-weight: 400\"><\/h2>\n<p style=\"font-weight: 400\">\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-arte-e-biologia\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#arte-e-biologia\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"arte-e-biologia\">\n\t\t\t\t\t\t\t<h3>Arte e Biologia<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"arte-e-biologia\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p style=\"font-weight: 400\">O laborat\u00f3rio tem uma longa tradi\u00e7\u00e3o no acolhimento de artistas visuais para explorar a interse\u00e7\u00e3o entre arte e ci\u00eancias biom\u00e9dicas (com especial enfoque na arte e imunologia), com trabalhos exibidos internacionalmente em cidades como Linz, Nova Iorque, Pequim, Berlim, Dublin, Toronto, S\u00e3o Petersburgo, Amsterd\u00e3o e Lisboa.<\/p>\n<p style=\"font-weight: 400\">Marta de Menezes (https:\/\/martademenezes.com) \u00e9 Artista Associada do laborat\u00f3rio e coordena o programa art\u00edstico.<\/p>\n<p>&nbsp;<\/p>\n<h2 style=\"font-weight: 400\">Artistas Seleccionados e Projetos:<\/h2>\n<ul>\n<li style=\"font-weight: 400\">Marta de Menezes \u2013 projetos em imunidade: <a href=\"https:\/\/martademenezes.com\/art\/immunity\/\">https:\/\/martademenezes.com\/art\/immunity\/<\/a><\/li>\n<li style=\"font-weight: 400\">Nigel Helyer: <a href=\"https:\/\/www.sonicobjects.com\/\">https:\/\/www.sonicobjects.com<\/a><\/li>\n<li style=\"font-weight: 400\">Andrew Carnie: <a href=\"https:\/\/www.andrewcarnie.uk\/\">https:\/\/www.andrewcarnie.uk<\/a><\/li>\n<li style=\"font-weight: 400\">Whitefeather Hunter: <a href=\"https:\/\/www.whitefeatherhunter.ca\/\">https:\/\/www.whitefeatherhunter.ca<\/a><\/li>\n<li style=\"font-weight: 400\">Guy Ben-Ary: <a href=\"https:\/\/guybenary.com\/\">https:\/\/guybenary.com<\/a><\/li>\n<li style=\"font-weight: 400\">Rudolfo Quintas: <a href=\"https:\/\/cultivamoscultura.com\/2024\/11\/11\/residency-by-rudolfo-quintas-8-to-22-november\/\">https:\/\/cultivamoscultura.com\/2024\/11\/11\/residency-by-rudolfo-quintas-8-to-22-november\/<\/a><\/li>\n<li style=\"font-weight: 400\">Oron Catts and Ionat Zurr: <a href=\"https:\/\/cultivamoscultura.com\/2023\/12\/19\/residency-by-ionat-zurr-oron-catts-december-2023\/\">https:\/\/cultivamoscultura.com\/2023\/12\/19\/residency-by-ionat-zurr-oron-catts-december-2023\/<\/a><\/li>\n<li style=\"font-weight: 400\">Untammed complexity: Exposi\u00e7\u00e3o art\u00edstica de projetos do laborat\u00f3rio no Congresso Europeu de Imunologia em Dublin (2024): <a href=\"https:\/\/cultivamoscultura.com\/2024\/08\/28\/enlightten-untamed-complexity-31-aug-2-sept-dublin-2024\/\">https:\/\/cultivamoscultura.com\/2024\/08\/28\/enlightten-untamed-complexity-31-aug-2-sept-dublin-2024\/<\/a><\/li>\n<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t<div class=\"accordion-item\">\n\t\t\t\t\t<h2 class=\"accordion-header\" id=\"header-links-uteis\">\n\t\t\t\t\t\t<button class=\"accordion-button collapsed\" type=\"button\" data-bs-toggle=\"collapse\"\n\t\t\t\t\t\t\tdata-bs-target=\"#links-uteis\"\n\t\t\t\t\t\t\taria-expanded=\"false\" aria-controls=\"links-uteis\">\n\t\t\t\t\t\t\t<h3>Links \u00dateis<\/h3>\n\t\t\t\t\t\t<\/button>\n\t\t\t\t\t<\/h2>\n\t\t\t\t\t<div id=\"links-uteis\" class=\"accordion-collapse collapse\"\n\t\t\t\t\t\tdata-bs-parent=\"#accordion\">\n\t\t\t\t\t\t<div class=\"accordion-body\">\n\t\t\t\t\t\t\t<p><span style=\"text-decoration: underline\">ORCID:<\/span> https:\/\/orcid.org\/0000-0001-6935-8500<\/p>\n<p>&nbsp;<\/p>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\n<\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/section>\n\t<\/div>\n\n<\/div>","protected":false},"featured_media":0,"template":"","acf":{"header_image":false,"ongoing_projects":"","selected_publications":"","useful_links":"","awards":"","funding":"","sponsorship":"","extra_information":false,"location":"Lisboa","subtitle":"Regula\u00e7\u00e3o dos linf\u00f3citos","team_leader":[{"ID":8332,"post_author":"1004","post_date":"2025-05-27 13:42:52","post_date_gmt":"2025-05-27 13:42:52","post_content":"","post_title":"Lu\u00eds Gra\u00e7a","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"luis-ricardo-simoes-da-silva-graca","to_ping":"","pinged":"","post_modified":"2026-03-13 10:02:05","post_modified_gmt":"2026-03-13 10:02:05","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/luis-ricardo-simoes-da-silva-graca\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"}],"order":"170","is_external":false,"related_research_areas":[1499],"lab_members":[{"ID":8116,"post_author":"1004","post_date":"2025-05-27 13:43:22","post_date_gmt":"2025-05-27 13:43:22","post_content":"","post_title":"Vladimir Ghilas","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"vladimir-ghilas","to_ping":"","pinged":"","post_modified":"2026-04-16 11:40:53","post_modified_gmt":"2026-04-16 11:40:53","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/vladimir-ghilas\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7789,"post_author":"1004","post_date":"2025-05-27 13:44:07","post_date_gmt":"2025-05-27 13:44:07","post_content":"","post_title":"Beatriz Guerreiro Filipe","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"beatriz-guerreiro-filipe","to_ping":"","pinged":"","post_modified":"2026-04-16 11:47:53","post_modified_gmt":"2026-04-16 11:47:53","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/beatriz-guerreiro-filipe\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7792,"post_author":"1002","post_date":"2025-05-27 13:44:07","post_date_gmt":"2025-05-27 13:44:07","post_content":"","post_title":"Deepanwita Ghosh","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"deepanwita-ghosh","to_ping":"","pinged":"","post_modified":"2025-05-27 13:44:07","post_modified_gmt":"2025-05-27 13:44:07","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/deepanwita-ghosh\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7777,"post_author":"1002","post_date":"2025-05-27 13:44:08","post_date_gmt":"2025-05-27 13:44:08","post_content":"","post_title":"Diogo Martins Fonseca","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"diogo-martins-fonseca","to_ping":"","pinged":"","post_modified":"2025-05-27 13:44:08","post_modified_gmt":"2025-05-27 13:44:08","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/diogo-martins-fonseca\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7780,"post_author":"1004","post_date":"2025-05-27 13:44:08","post_date_gmt":"2025-05-27 13:44:08","post_content":"","post_title":"Elisa Mastrantuono","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"elisa-mastrantuono","to_ping":"","pinged":"","post_modified":"2026-04-16 11:47:24","post_modified_gmt":"2026-04-16 11:47:24","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/elisa-mastrantuono\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7783,"post_author":"1004","post_date":"2025-05-27 13:44:08","post_date_gmt":"2025-05-27 13:44:08","post_content":"","post_title":"Jean-Christophe Lone","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"jean-christophe-lone","to_ping":"","pinged":"","post_modified":"2026-04-16 11:42:36","post_modified_gmt":"2026-04-16 11:42:36","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/jean-christophe-lone\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7768,"post_author":"1004","post_date":"2025-05-27 13:44:09","post_date_gmt":"2025-05-27 13:44:09","post_content":"","post_title":"Maria Miguel Cavaco","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"maria-miguel-cavaco","to_ping":"","pinged":"","post_modified":"2026-04-16 11:44:13","post_modified_gmt":"2026-04-16 11:44:13","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/maria-miguel-cavaco\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7771,"post_author":"1002","post_date":"2025-05-27 13:44:09","post_date_gmt":"2025-05-27 13:44:09","post_content":"","post_title":"Pedro Gaspar","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"pedro-gaspar","to_ping":"","pinged":"","post_modified":"2025-05-27 13:44:09","post_modified_gmt":"2025-05-27 13:44:09","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/pedro-gaspar\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7774,"post_author":"1004","post_date":"2025-05-27 13:44:09","post_date_gmt":"2025-05-27 13:44:09","post_content":"","post_title":"Rui Pedro Oliveira Do Amaral Vieira","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"rui-pedro-oliveira-do-amaral-vieira","to_ping":"","pinged":"","post_modified":"2026-03-12 09:59:24","post_modified_gmt":"2026-03-12 09:59:24","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/rui-pedro-oliveira-do-amaral-vieira\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7411,"post_author":"1002","post_date":"2025-05-27 13:45:14","post_date_gmt":"2025-05-27 13:45:14","post_content":"","post_title":"Ana Raquel Maceiras Oliveira","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"ana-raquel-maceiras-oliveira","to_ping":"","pinged":"","post_modified":"2025-05-27 13:45:14","post_modified_gmt":"2025-05-27 13:45:14","post_content_filtered":"","post_parent":0,"guid":"https:\/\/gimm.pt\/people\/ana-raquel-maceiras-oliveira\/","menu_order":0,"post_type":"people","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":7414,"post_author":"1002","post_date":"2025-05-27 13:45:14","post_date_gmt":"2025-05-27 13:45:14","post_content":"","post_title":"Filipa Ramos De 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