Project JAGUAR: mapping immune cell diversity across Latin America

CARLA JONES; ANNA LORENC; TARRAN RUPALL; THAIS DE OLIVEIRA; MAXIMILIANO BERRO CASTIGLIONI; LUIS ALBERTO TATAJE LAVANDA; BENILTON DE SÁ CARVALHO; MARCELA KATHERINE SJÖBERG HERRERA; ROMAGNOLI PA; YESID CUESTA ASTROZ; ALEJANDRA MEDINA RIVERA; GOSIA TRYNKA

Belfast

Congreso; British Society for Immunology Congress 2023; 2023

British Society of Immunology

Genetic variation impacts the composition of the immune system; it affects cell proportions and regulates gene expression within different cell types. Importantly, genetic variation also regulates gene expression changes as cells undergo activation. Consequently, this shapes a range of immune cell phenotypes, from time of response to type and magnitude of effector functions, ultimately defining the response of the immune system. As a result, susceptibility and severity to infections, e.g. COVID-19, and the prevalence of autoimmune and inflammatory diseases varies across populations.Yet the predominant amount of functional immuno-genomic studies and genome-wide association studies for disease susceptibility have been conducted in Europeans. Project JAGUAR emerges as a coordinated Latin American endeavour to expand this region’s chapter within the Human Cell Atlas initiative and population-scale immuno-genomics studies. Latin American populations result from genetic and cultural admixture among European, Indigenous, African and Asian groups, additionally shaped by the rich diversity of ecosystems and population migrations. Our goal is to address how regional genetic diversity adapts to environmental factors shaping the immune cell landscape and resulting in differences in the individual’s responses to infections and their susceptibility to developing autoimmune and inflammatory diseases. We aim to define the diverse composition of peripheral blood mononuclear cells in 1,080 healthy individuals from seven distinct countries in Latin America, recruiting from different areas, including urban Mexico City to the Brazilian Amazon Forest. We are leveraging a range of single-cell omics technologies (scATAC-seq, scRNA-seq, CITE-seq and TCR/BCR-seq) to derive a multi-modal, highly detailed map of immune cell states and identify how genetic variants regulate gene expression and the composition of immune cells across diverse ancestries. This represents a remarkable opportunity to deepen our understanding of genetic and environmental influences on all human traits.