Cryptopatches Are Essential for the Development of Human GALT

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 novel observation represents a fundamental breakthrough in our mechanistic understanding of the role of cryptopatches in human GALT genesis and emphasizesthe evolutionary conservation of this developmental process between humans and mice. 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 in humans. This human-mouse chimeric model represents the most comprehensive experimental platform currently available for the study and the pre-clinical efficacy testing of therapeutics designed to repair disease-damaged GALT