Luisa Cervantes-Barragan, PhD

ARTDTP Research Discipline:

Mucosal immune system-microbiota interactions

The gastrointestinal tract is one of the primary sites of exposure to pathogens, but it is also the niche of the largest collection of commensal microbes in the body. Studies in the recent years started to reveal the extensive influence that microbiota and intestinal immune system have on each other and how this constant interplay impacts immune responses to pathogens and the development of chronic inflammation. The study of this very dynamic interaction is the main focus of our lab. Using in vivo models harboring different microbiota as well as using diverse agents to perturb microbiota homeostasis, we can determine which immune cell populations are affected by the presence or absence of microbial species or their metabolic products, as well as discover new microbiota- immune system interactions. Moreover, using genetically modified models we can study the function of these immune populations or molecules expressed on them, and how they impact our ability to control pathogens or preserve the intestinal barrier.

Recently, using these approaches we discovered how a population of intraepithelial T cells, the CD4+CD8αα+ T cells (DP IEL); require the presence of Lactobacillus reuteri to develop. We showed that CD4 intraepithelial T cells use the Aryl hydrocarbon receptor (AhR) to sense indole-3-lactic acid, produced by L. reuteri metabolism of dietary tryptophan, to convert into DP IELs1. Furthermore, using genetically modified models we could determine that CRTAM, an adhesion molecule expressed on DP IELs, is essential for their permanence at the epithelial cell layer2. While intraepithelial T cells are some of the most abundant immune cell populations that reside in the intestine, and their location at the epithelial cell layer makes them some of the first to interact with microbiota, pathogens and dietary antigens, the function and mechanism of action of some of these T cells populations, like the DP IELs is largely unknown. We aim to discover the role of this population in intestinal homeostasis, response to pathogens or control of inflammation, and to discover novel interactions between intestinal microbiota members and immune populations in the intestinal intraepithelial space.

1 Cervantes-Barragan L. et al . Science 2018.
2 Cortez VS, Cervantes-Barragan L. et al. JEM 2014.