Luís Graça Lab

Group leader

Luís Graça

Group Leader

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Lymphocyte Regulation

Our group studies how immune responses are regulated. We dissect the mechanisms maintaining immune homeostasis, allowing efficient protection against infection without inflammation and tissue damage. Knowing how the immune balance is maintained enables the development of methods to alter this balance therapeutically: reducing immunity when the immune system is causing damage, such as in autoimmunity, allergy, and transplant rejection, or enhancing the immune response to boost vaccines or the action against infection or cancer.

We study lymphocytes that regulate immune responses, such as T regulatory and T follicular regulatory cells. We are interested in the regulation of germinal center responses, T follicular helper cells, and antibody production. Cutting-edge single-cell and spatial multiomics and computational methods are critical to probing the biology of clinical samples in health and disease.

In the foreseeable future, therapeutic strategies to modulate the immune system will improve the quality of life of people suffering from immune-mediated diseases.

Funders

Regulatory T cells and Immune tolerance
The biology of germinal centres, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells and the regulation of antibody production
Clinical Research
Autoimmunity
Allergy
Transplantation
Vaccines
Infection and Immunity
Computational biology and bioinformatics
Epidemiology

2024/2027: ERC-Portugal: Finding the biological pathway connecting immune dysregulation and oncogenesis in Sjogren’s disease. Coordenação: Luís Graça. Agência Financiadora: Fundação para a Ciência e a Tecnologia (Lisboa, PT).

2023/2026: Modulation of human antibody responses by T follicular helper subsets. Coordenação: Luís Graça. Agência Financiadora: Fundação para a Ciência e a Tecnologia (Lisboa, PT).

2024/2025: Ending COVID-19 variants of concern through cohort studies (END-VOC). Coordenação de WP: Luís Graça. Agência Financiadora: European Union, Horizon 101046314.

2024/2025: Immu3Dorg-unveiling immune system dynamics in disease: exploiting 3D human organoids for drug testing. Coordenação: Diana Matias. CTI-Centro de Tecnologia e Inovação IMM (Lisbon, PT).

2023/2025: Reconstructing immune dysregulation leading to therapeutic resistance in Crohn’s disease. Coordenação: Luís Graça. Agência Financiadora: Merck Sharp and Dohme (Rahway, NJ, US).

2022/2026: PolyMuTEs- Polymeric nanoparticles-based multivalent mABs against glioblastoma for T-cell engagement. Coordenação: Diana Matias. Agência Financiadora: Fundação “la Caixa” (Barcelona, ES).

2022/2025: Harnessing germinal centre regulation for improved vaccines. Coordenação: Luís Graça. Agência Financiadora: Fundação “la Caixa” (Barcelona, ES).

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. (2024) Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue. Cell Discov. 10:64. https://doi.org/10.1038/s41421-024-00681-0

Malato J, Ribeiro RM, Leite PP, Casaca P, Antunes C, Fonseca VR, Gomes MC, Graca L. (2023) Stability of hybrid versus vaccine immunity against BA.5 infection over 8 months. Lancet Infect Dis. 23:148–150.

Malato J, Ribeiro RM, Leite PP, Casaca P, Fernandes E, Antunes C, Fonseca VR, Gomes MC, Graca L. (2022) Risk of BA.5 infection in individuals exposed to prior SARS-CoV-2 variants. N Engl J Med.https://doi.org/10.1056/NEJMc2209479

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. (2021) Developmental bifurcation of human T follicular regulatory cells. Sci Immunol. 6:eabd8411.

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. Nat Rev Rheumatol. 15:475. (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. Sci 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. Nat Commun. 8:15067.

Oliveira VG, Agua-Doce A, Curotto de Lafaille MA, Lafaille JJ, Graca L. (2013) Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice through a Foxp3-independent mechanism that relies on IL-10. Blood121:3936–3945.

Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira VG, Faro J, Graca L. (2011) Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol. 187:4553–4560.

A complete list of publications can be found here.

2023: Prémio Pfizer em Investigação Clínica; Pfizer / Sociedade das Ciências Médicas de Lisboa.

2023: Medalha de Mérito da Freguesia de Alvalade.

2019: Research Excellence Award. Prémios Científicos Caixa Geral de Depósitos/Universidade de Lisboa.

2017: iMM Innovators, TwinToInfect.

2011: NEDAI Prize in Autoimmunity Research.

2010: Young Entrepreneur Award 2010, National Society of Entrepreneurship (ANJE).

2010: National Innovation Award for Health Technologies; Banco Espirito Santo (BES).

2009: Prof. Heimburger Award in Coagulation Diseases, CSL Behring.

Luis Graca chairs the National Immunization Technical Advisory Committee for seasonal vaccination against influenza and COVID-19.

The laboratory has a long standing tradition in hosting visual artists to explore the intersection of art and biomedical sciences (with an emphasis on art and immunology), with outcomes exhibited internationally in cities such as Linz, New York, Beijing, Berlin, Dublin, Toronto, St. Petersburg, Amsterdam, and Lisbon.

Marta de Menezes (https://martademenezes.com) is Associate Artist at the laboratory, and curates the art program.