Figure 2.

LIGHT in intestinal inflammation. The physiologic function of the LTβR pathway maintains the organization of secondary lymphoid organs (Peyer’s patches, spleen, lymph nodes) and also plays a key role in formation of tertiary lymphoid structures at sites of persistent inflammation. Innate pathogen-sensing receptors stimulate neutrophil and NK cell secretion of LIGHT at sites of inflammation. LIGHT activates LTβR to differentiate stromal cells into an immune niche favoring activation of antigen-presenting macrophages (MAC) and dendritic cells (DC) to recruit T and B cells. LIGHT activates the HVEM pathway to promote rapid recall responses and formation of germinal centers where T follicular helper cells (Tfh) promote antibody production by B cells. In patients with IBD, persistent intestinal inflammation may occur from a reinforcing cycle of LIGHT secretion by innate effector cells following disruption in the integrity of the mucosal epithelial barrier and re-exposure of T cells to self-antigens.