Innate lymphoid cells; promoting homeostasis and preventing gut dysbiosis (360G-Wellcome-204721_Z_16_Z)

I propose to examine the hypothesis that innate lymphoid cells (ILCs) mediate crosstalk between the intestinal microbiota and the reconstituting adaptive immune system in a cohort of children with primary immunodeficiency disorders undergoing haematopoietic stem cell transplantation (HSCT). I will use mass cytometry to examine the reconstitution of leukocyte populations after HSCT in a longitudinal fashion. I will characterise the peripheral blood ILC compartment in detail, including expression of activation markers, chemokine receptors and cytokines by ILC subsets ex vivo. I will measure gut bacterial diversity in longitudinally collected faecal samples and assess markers of microbial translocation. These immune and microbial parameters will be correlated with clinical features in a multi-dimensional statistical model to identify risk factors for HSCT outcomes such as graft-versus-host disease (GVHD) and gut failure. Further analysis of ILC function will be performed through in vitro studies of these immune populations to examine how they can regulate T cell responses. The impact of microbial signals and cytokines on ILC regulation of T cells will be assessed. A better understanding of ILC function in the context of immunodeficiency and HSCT may help us to develop strategies to avoid immune complications such as GVHD in some transplant recipients.