Fetal lymphoid tissue inducer (LTi) cells have been shown to be involved in the lymphoid organ development. A similar population of cells, termed LTi-like cells, is
located in the adult intestinal lamina propria and supports the organization of gut-associated lymphoid tissue (GALT). The function of LTi and LTi-like cells is dependent on the transcription factor retinoid-related orphan receptor (ROR)γt. ROR gamma t-deficient mice lack lymph nodes and various organized GALT.
We are investigating the role of RORγt for the immune reconstitution after hematopoietic stem cell transplantation (HSCT) as a potential approach for enhancing T cell immunity.
Activated T cells such as those found in GVHD express adhesion molecules for immigration to specific extra-lymphoid tissues. Gut-homing T cells express CCR9 and
respond to its sole ligand CCL25, which is expressed by intestinal epithelial cells. We are therefore investigating the role of CCR9 in intestinal GVHD including the therapeutic potential of CCR9 targeting strategies to prevent or treat gut GVHD. A
CCR9-specific antagonist with equal potency against human and murine CCR9 is currently tested in a Phase III trial for inflammatory bowel disease.
