Immune profiling of human gut-associated lymphoid tissue identifies a role for isolated lymphoid follicles in the priming of region-specific immunity

The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a novel method for identifying and isolating human gut associated lymphoid tissues (GALT) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILF and M-ILF), as well as GALT-free intestinal lamina propria (LP). SM-ILF and M-ILF showed distinct patterns of distribution along the length of the intestine, were linked to the systemic circulation through MAdCAM-1+ high endothelial venules and efferent lymphatics and had an adaptive immune cell profile consistent with immune inductive sites that was highly distinct from GALT-free LP. IgA sequencing analysis indicated that human ILF are the sites where intestinal adaptive immune responses are initiated in an anatomically restricted manner. Collectively, our results position ILF as key inductive hubs for regional immunity in the human intestine and the novel methods presented will allow future assessment of these enigmatic immune niches in health and disease.