Modulating the intestinal immune system: the role of lymphotoxin and GALT organs

The gut associated immune system fences off potentially harmful intestinal antigens from the systemic circulation and induces systemic tolerance against luminal antigens. Intestinal immune responses against luminal antigens include IgA secretion and induction of regulatory cells. Unlike few other cytokines, lymphotoxin alpha/beta regulates the development of intestinal lymphoid organs. The embryonic development of Peyer's patches, postnatal lamina propria B cell development, and isolated lymphoid follicle development all depend on lymphotoxin beta receptor interactions. Lymphotoxin alpha/beta signalling also contributes to the development of mesenteric lymph nodes. In addition, intestinal inflammation is suppressed by inhibition of lymphotoxin beta signalling, an observation which has initiated clinical studies using this treatment principal. Intestinal follicular lymphoid organs are sites of antigen presentation. Antigen presenting cells tune the delicate balance between intestinal immune tolerance and inflammation. Therefore, gut associated lymphatic organs and factors regulating their development are critical for the prevention of adverse immune reactions to intestinal antigens. This review provides an overview on the role of lymphotoxin and the gut associated lymphatic organs in the regulation of oral tolerance and intestinal inflammation.