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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 α/β 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 β receptor interactions. Lymphotoxin α/β signalling also contributes to the development of mesenteric lymph nodes. In addition, intestinal inflammation is suppressed by inhibition of lymphotoxin β 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.
INTRODUCTION
Intestinal mucosal surfaces are exposed to alimentary and bacterial antigens of the intestinal flora. The physiological immune response towards intestinal antigens is non-harmful to the entire organism and includes induction of systemic immune tolerance and IgA secretion. Inflammatory bowel disease (IBD) is associated with activation of the local intestinal and systemic immune responses. In various animal models of IBD, uncontrolled immune responses following intestinal injury result in mucosal insult. Colitis is associated with loss of tolerance against intestinal antigens, which also contributes to perpetuation of local and systemic inflammatory immune responses. Characterisation of intestinal inflammatory cytokine pathways has provided valuable tools to modulate the activity of IBD.
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