The interplay between diet, immune cells and intestinal microbes ensures vital functions of the organism, such as energy and micronutrient extraction from the diet, protection from pathogenic microbes and maintenance of a healthy epithelial barrier. These complex networks are of vital importance to organismic homeostasis, while inadequate relationships can lead to cancer and chronic inflammatory diseases, which are major Public Health concerns.
Adaptive immune lymphocytes express recombining antigen-specific receptors. These lymphocytes are activated by defined antigens and require a differentiation phase before exerting their effector function. In contrast, innate lymphocytes display rapid effector functions despite their set of limited germ-line encoded receptors. A mounting body of evidence indicates that in addition to their well-established developmentally regulated program, immune cells are also controlled by dietary signals and neuronal inputs. Thus, although there is tangible evidence suggesting that immune cells possess unexpected sensing strategies, how lymphoid cells perceive, integrate and respond to environmental cues remains poorly understood and vastly unexplored.
We centre our efforts on defining lymphocyte sensory mechanisms in health and disease. We use an integrative across-level approach aiming to elucidate the tenets of lymphocyte sensing and communication, within, across and beyond the organism.

Projects

Our long-term goal is to understand sensory and communication pathways that determine immune cell fate and disease progression. To achieve this, we centre our efforts at mucosal barriers that constitute the largest interface of the body with the external environment. Epithelial barriers line body surfaces and grant safeguard against harmful pathogens but are frequent targets of oncologic transformation and chronic inflammatory diseases. In this context, we tackle the following hitherto elusive points:

Micronutrient sensing by lymphocytes: we aim to unravel the mechanisms by which micronutrients control mucosal lymphocytes and their interaction with the epithelial barrier and microbiota.

Multi-tissue sensors: we focus on novel sensing programs by which lymphocytes integrate neuron and neuroglia cues, defining key multi-cellular units at the core of mucosal physiology in health and disease.

Neuronal circuits and circadian inputs: we focus on how neuronal circuits and their inputs regulate immune functions in the context of chronic inflammation and cancer.

Henrique Veiga-Fernandes, PhD
Principal Investigator
henrique.veigafernandes@research.fchampalimaud.org

Biography

Helder Ribeiro

helder.ribeiro@research.fchampalimaud.org

Miguel Rendas
Research Technician
miguel.rendas@research.fchampalimaud.org

Lab Administration

Telma Carrilho
Lab Administrator
telma.carrilho@research.fchampalimaud.org

Veiga-Fernandes H, Freitas AA (2017) The S(c)ensory Immune System Theory Trends in Immunology (doi:10.1016/j.it.2017.02.007)

Veiga-Fernandes H, Pachnis V (2017) Neuroimmune regulation during intestinal development and homeostasis Nat Immunol 18 (2), 116-122 (doi:10.1038/ni.3634)

Ibiza S, García-Cassani B, Ribeiro H, Carvalho T, Almeida L, Marques R, Misic AM, Bartow-McKenney C, Larson DM, Pavan WJ, Eberl G, Grice EA, Veiga-Fernandes H. (2016) Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence Nature 535 (7612), 440–443 (doi:10.1038/nature18644)

Veiga-Fernandes H, Mucida D. (2016) Neuro-Immune Interactions at Barrier Surfaces. Cell 165 (4), 801-811 (doi:10.1016/j.cell.2016.04.041)

Veldhoen M, Veiga-Fernandes H (2015) Feeding immunity: skepticism, delicacies and delights. Nat Immunol 16 (3), 215-219 (doi:10.1038/ni.3100)

Fonseca-Pereira D, Arroz-Madeira S, Rodrigues-Campos M, Barbosa IA, Domingues RG, Bento T, Almeida AR, Ribeiro H, Potocnik AJ, Enomoto H, Veiga-Fernandes H. (2014) The neurotrophic factor receptor RET drives haematopoietic stem cell survival and function Nature 514 (7520), 98-101 (doi:10.1038/nature13498)

Klose CS, Flach M, Möhle L, Rogell L, Hoyler T, Ebert K, Fabiunke C, Pfeifer D, Sexl V, Fonseca-Pereira D, Domingues RG, Veiga-Fernandes H7, Arnold SJ, Busslinger M, Dunay IR, Tanriver Y, Diefenbach A. (2014) Differentiation of Type 1 ILCs from a Common Progenitor to All Helper-like Innate Lymphoid Cell Lineages Cell 157 (2), 340-356 (doi:10.1016/j.cell.2014.03.030)

van de Pavert SA, Ferreira M, Domingues RG, Ribeiro H, Molenaar R, Moreira-Santos L, Almeida FF, Ibiza S, Barbosa I, Goverse G, Labao-Almeida C, Godinho Silva C, Konijn T, Schooneman D, O Toole T, Mizee MR, Habani Y, Haak E, Santori FR, Littman DR, Schult (2014) Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity Nature 508 , 123-127 (doi:10.1038/nature13158)