title: Cryptopatches are essential for the development of human GALT.
abstract: Abnormal gut-associated lymphoid tissue (GALT) in humans is associated with infectious and autoimmune diseases, which cause dysfunction of the gastrointestinal (GI) tract immune system. To aid in investigating GALT pathologies in vivo, we bioengineered a human-mouse chimeric model characterized by the development of human GALT structures originating in mouse cryptopatches. This observation expands our mechanistic understanding of the role of cryptopatches in human GALT genesis and emphasizes the evolutionary conservation of this developmental process. Immunoglobulin class switching to IgA occurs in these GALT structures, leading to numerous human IgA-producing plasma cells throughout the intestinal lamina propria. CD4+ T cell depletion within GALT structures results from HIV infection, as it does in humans. This human-mouse chimeric model represents the most comprehensive experimental platform currently available for the study and for the preclinical testing of therapeutics designed to repair disease-damaged GALT.
authors.affiliation: Division of Infectious Diseases, Center for AIDS Research, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Paul W
authors.initials: PW
authors.lastname: Denton
authors.forename: Angela
authors.initials: A
authors.lastname: Wahl
authors.forename: J Victor
authors.initials: JV
authors.lastname: Garcia
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000254:growth & development / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000254:growth & development / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000254:growth & development / Q000276:immunology*; D051379:Mice