Scientific team headed by Luís Graça, leading a Portuguese research group at iMM, uncovers how antibody production is controlled in different contexts, opening doors for new allergy treatments without compromising immune defense

Antibodies play a crucial role in defending our bodies against infections, and their production is meticulously controlled by a specialized type of immune cells called follicular helper lymphocytes. A research group led by Luís Graça, group leader at Instituto de Medicina Molecular João Lobo Antunes (iMM) and professor at the University of Lisbon's Faculty of Medicine, has delved into the intricate workings of these cells. In an article featured in the esteemed journal Cell Discovery, the team reveals that these follicular helper lymphocytes can be split into two distinct groups: one dedicated to producing antibodies that fight viral infections, and another linked to antibody production in response to parasites and allergies. This newfound understanding could lead to the development of innovative therapies targeting allergic conditions, without compromising the body's immune defense against infections.

“We employed computational biology to pinpoint the genes activated in follicular helper lymphocytes involved in producing both categories of antibodies,” says Saumya Kumar, a co-first author of the paper. "By utilizing artificial intelligence, we could categorize the genes associated with antibodies that defend against viral infections versus those that respond to parasites and allergies,” Kumar continues. “Armed with this data, we used cutting-edge microscopy to match active gene data with the physical location of these cells within the body. As a result, we discovered that the cells, which our computational models tied to viral infections, indeed appear when there is an actual viral invasion,” adds Afonso Basto, also a co-first author.

Luís Graça emphasizes the potential of their findings, stating, “These insights unveil new molecular targets for therapies aimed at regulating the production of antibodies, especially in diseases such as allergies and autoimmune disorders. In theory, this could allow us to decrease the production of harmful antibodies linked to these diseases while preserving the immune system’s ability to produce essential antibodies to combat viruses.” He further explains, “It was as though previously, all these cells were hidden in a sealed bag. Whenever antibody responses malfunctioned, we had no understanding of what was happening inside. Now, that bag has been opened, and we can start to decode the functioning of these distinct cell groups independently.”

The success of this research hinged on the collaboration of experts across multiple fields including medicine, biology, and computational sciences. This interdisciplinary approach was critical to gaining a comprehensive understanding of how these immune cells function in both health and disease. As Graça puts it, “Scientific teams today resemble orchestras where each specialist plays a unique instrument in harmony.”

Contacts:

Luís Graça

Group Leader, iMM

Email: [email protected]

Helena Pinheiro

Science Communication, iMM

Email: [email protected]

Reference:

*Saumya Kumar, Afonso P Basto, Filipa Ribeiro, Silvia CP Almeida, Patricia Campos, Carina Peres, Nadia Pulvirenti, Sarwah Al-Khalidi, Anna Kilbey, Jimena Tosello, Eliane Piaggio, Momtchilo Russo, Margarida Gama-Carvalho, Seth B. Coffelt, Ed W Roberts, Jens Geginat, Helena F Florindo, Luis Graca (2024) "Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue." Cell Discovery. https://doi.org/10.1038/s41421-024-00681-0

This work was conducted at the João Lobo Antunes Institute of Molecular Medicine in collaboration with researchers from institutions such as the Gulbenkian Institute of Science, CIISA - Center for Interdisciplinary Research in Animal Health, the Associated Laboratory for Animal and Veterinary Science (AL4AnimalS), iMed.ULisboa, the Nazionale di Genetica Molecolare (Italy), the UK Institute of Cancer Sciences, Cancer Research UK, Institut Curie (France), Institute of Biomedical Sciences (Brazil), BioISI – Biosystems & Integrative Sciences Institute, and the Università degli studi di Milano (Italy).

Journal

Cell Discovery

DOI

10.1038/s41421-024-00681-0

Method of Research

Experimental Study

Subject of Research

Animals

Article Title

Specialized Tfh cell subsets driving type-1 and type-2 humoral responses in lymphoid tissue.

Article Publication Date

June 4, 2024