Regulation of functional differences between cord blood versus adult peripheral blood innate cells. (LSBR 1128)
Prof. Dr. Reina E. Mebius, Dept. of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam
Postdoc investigator: Antonio Baptista PhD (Jul. 2012 – Apr. 2014)
Ph.D. student: Yotam Bar-Ephraim (Apr. 2014 – Jun. 2015)
Technician: Tanja Konijn (Apr. 2014 – Jun. 2015)
In this project we focused on a small subset of immune cells, the so called innate lymphoid cells, which are best studied when derived from human tonsils. These cells have been described to be important for maintaining tissue integrity, in particular within tissues that are in direct contact with the outside world, such as the skin and the gut. In addition, upon tissue damage, these innate lymphoid cells are thought to be important for tissue regeneration. These cells can produce the factors that T lymphocytes normally generate, and are therefore important for our defense against micro-organisms. We have investigated whether they are present within peripheral blood of adult individuals as well as in cord blood.
Our data show that these cells, when found in adult peripheral blood or cord blood, are unable to produce the factors that are needed for defense against invading micro-organisms. Rather, these immune cells need to first receive a proper stimulus, after which they subsequently differentiate towards cells that can produce these factors. Our data furthermore show that innate lymphoid cells have the capacity to recirculate through the body, going from peripheral blood to Iymph nodes and back to the blood, in search of stimuli produced by bacteria or viruses. When e.g. bacteria enter our body via the skin, they will be taken up by specialized immune cells within the skin, and are then transported in little pieces to the draining lymph nodes. Here, lymphocytes will become activated in such a way, that these cells will help to eliminate the bacteria. We now show that in addition to lymphocytes, also these innate lymphoid cells are most likely exposed to inflammatory stimuli within these Iymph nodes, which will direct their further stimulation into effector cells. We hypothesize that these effector innate lymphoid cells will, upon appropriate differentiation, migrate to the site where the bacteria entered the skin and help to combat the invaders, while additionally restoring tissue integrity. We furthermore found that innate lymphoid cells have the capacity to interact with T lymphocytes directly and by doing so they may have the capacity to influence the response of these lymphocytes. Further studies will have to reveal whether these effects are either suppressing or activating these T lymphocytes.