Intestinal lymphoid tissues: is variety an asset or a liability?

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Abstract
Advances in our understanding of lymphoid tissue development has led to an appreciation of the variety of these structures in the intestinal mucosa. This knowledge has translated into more critical analysis of the function of mucosal lymphoid tissues and may lead to manipulation of development of these structures as a therapeutic modality. This review summarizes recent progress in understanding the variety, formation, and function of these structures. The intestinal mucosa and submucosa contain three types of lymphoid tissues ranging from the developmentally determined Peyer's patches to the inflammatory derived tertiary lymphoid tissues. Intermediate to these is a unique lymphoid tissue, isolated lymphoid follicles, which shares properties of both Peyer's patches and tertiary lymphoid tissues. In the healthy intestine, Peyer's patches and isolated lymphoid follicles generate protective and homeostatic immune responses. During chronic inflammation, the function of the more inducible lymphoid tissues, isolated lymphoid follicles and tertiary lymphoid tissues, is unclear, but may include an ominous role propagating inappropriate responses and predisposing to malignancy. Understanding the variety of lymphoid tissues, how they function, and how they develop may offer strategies to manipulate these structures to optimize mucosal vaccines and treat intestinal inflammatory diseases.