title: Differential induction of isolated lymphoid follicles in the gut by 18β-glycyrrhetinic acid.
abstract: 18β-glycyrrhetinic acid (GRA) is a pharmacologically active component of licorice root with documented immunomodulatory properties. We reported that GRA administered orally to mice induces B cell recruitment to isolated lymphoid follicles (ILF) in the small intestine and shortens the duration of rotavirus antigen shedding. ILF are dynamic lymphoid tissues in the gut acquired post-natally upon colonization with commensal bacteria and mature through B cell recruitment to the follicles, resulting in up-regulation of IgA synthesis in response to changes in the composition of microbiota. In this study, we investigated potential mechanisms by which GRA induces ILF maturation in the ileum and the colon using mice depleted of enteric bacteria and a select group of mice genetically deficient in pattern recognition receptors. The data show GRA was unable to induce ILF maturation in ileums of mice devoid of commensal bacteria, MyD88-/- or NOD2-/- mice, but differentially induced ILF in colons. Increased expression of chemokine and chemokine receptor genes that modulate B and T cell recruitment to the mucosa were in part dependent on NOD2, TLR, and signaling adaptor protein MyD88. Together the results suggest GRA induces ILF through cooperative signals provided by bacterial ligands under normal conditions to induce B cell recruitment to ILF to the gut, but that the relative contribution of these signals differ between ileum and colon.
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Hendricks
authors.affiliation: Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Lowe
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
authors.forename: Michele E
authors.initials: ME
authors.lastname: Hardy
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000276:immunology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology
chemical_list: D018925:Chemokines; D007155:Immunologic Factors; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid