Regardless, there are sufficient data to support in vivo biological activity of GRA, making this an attractive compound to investigate for its ability to induce or modulate beneficial immune responses. Importantly, experimental evidence for activity in the intestine following oral delivery has been documented. There are significant advantages to orally administered compounds in the context of development of adjuvants and immunomodulatory therapeutics, and GRA has potential to function in this capacity. We reported that GRA administered orally to mice induces B cell recruitment to isolated lymphoid follicles in the gut and does so in the absence of 2-Methylserotonin maleate external antigenic stimulus. ILF are dynamic B cell-rich lymphoid tissues that, in contrast to secondary lymphoid tissues including Peyer��s Patches and lymph nodes, develop post-natally upon acquisition of commensal bacteria. ILF are present in both the small intestine and colon, and numbers of ILF increase in the ileum extending in to the colon as the concentration of bacteria increases distally. ILF consist of a spectrum of structures with size and cellular composition that is characteristic of maturation status. The number of ILF in the gut is invariant, but those present are morphologically dynamic, and thus have been collectively termed solitary isolated lymphoid tissue. SILT initially derive from cryptopatches, precursor structures located at the base of the crypts that are formed independently of bacterial colonization. ILF serve as Febrifugine dihydrochloride inductive sites for IgA synthesis, and their maturation to large B cell follicles occurs at least in part in response to changes in the composition of bacterial populations and some dietary ligands. ILF thus play a significant role in maintenance of intestinal inflammatory homeostasis by regulating mucosal IgA synthesis to control potentially damaging fluctuations in the microbiome. Signals that stimulate induction and maturation of ILF have been revealed through studies in knockout mice as well as germfree, and differentially colonized mice. Chemokines and chemokine receptors associated with B cell recruitment including CXCL13, CXCR5, CCL20 and CCR6 are important for ILF maturation in the ileum, as are receptor activator of NFkB ligand RANKL and b-defensin 3.