Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity

Thomas M. Fenton, Peter B. Jørgensen, Kristoffer Niss, Samuel J.S. Rubin, Urs M. Mörbe, Lene B. Riis, Clément Da Silva, Adam Plumb, Julien Vandamme, Henrik L. Jakobsen, Søren Brunak, Aida Habtezion, Ole H. Nielsen, Bengt Johansson Lindbom, William Winston Agace*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a method for isolating human gut-associated lymphoid tissues (GALTs) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILFs and M-ILFs, respectively) as well as in 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 immune profiles consistent with immune-inductive sites. IgA sequencing analysis indicated that human ILFs are sites where intestinal adaptive immune responses are initiated in an anatomically restricted manner. Our findings position ILFs as key inductive hubs for regional immunity in the human intestine, and the methods presented will allow future assessment of these compartments in health and disease.
Original languageEnglish
JournalImmunity
Volume52
Issue number3
Pages (from-to)557-570
ISSN1074-7613
DOIs
Publication statusPublished - 2020

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