Grant: Project Grant

In our intestine, there is a large cohort of microbes, including bacteria and fungi. Their presence is important for our immune system development. In germ-free mice (no microbes in the gut), lymph nodes in the host are small and incapable of mounting efficient responses against invading pathogens. For many years, we know this dependence of our immune system on those "microbial guests", but no molecular understanding was available. We previously found that a group of resident fungi called Candida tropicalis is critical for the peripheral lymph node maturation. The presence of these fungi in our gut microbiota drives a group of retinoic acid-producing dendritic cells (a type of immune cells) to leave the gut and come the growing lymph nodes, where they stimulate the structural development. They do so by inducing a particular set of molecules, PNAd, at the entry portal of lymph nodes. Interestingly, in the early weeks, lymphocytes entering those sites are educated to return to the gut to build the defense there first. This makes sense as the microbial burden is the heaviest in the gastrointestinal tract after birth. To follow up on those findings, we plan to study what types of fungal productions are driving these cells to leave the gut, and how these dendritic cells change the chemotaxis molecule expression in the peripheral lymph nodes. We also wish to study whether the homing of lymphocytes from the peripheral lymph nodes is critical to the initial gut immune homeostasis in the neonates. These questions are critical for us to comprehensively understand the interplays between our microbiota and the health of our immune system.