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 W. Agace

doi:10.1016/j.immuni.2020.02.001

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 W. Agace

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	557-570
Number of pages	21
Journal	Immunity
Volume	52
Issue number	3
DOIs	https://doi.org/10.1016/j.immuni.2020.02.001
Publication status	Published - 2020 Mar 17

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Subject classification (UKÄ)

Genetics and Genomics
Microbiology in the Medical Area

Free keywords

colon
human intestinal regional mucosal follicles
IgA
iIeum
ILF
PP

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10.1016/j.immuni.2020.02.001

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Fenton, T. M., Jørgensen, P. B., Niss, K., Rubin, S. J. S., Mörbe, U. M., Riis, L. B., Da Silva, C., Plumb, A., Vandamme, J., Jakobsen, H. L., Brunak, S., Habtezion, A., Nielsen, O. H., Johansson-Lindbom, B., & Agace, W. W. (2020). Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity. Immunity, 52(3), 557-570. https://doi.org/10.1016/j.immuni.2020.02.001

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

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.",

keywords = "colon, human intestinal regional mucosal follicles, IgA, iIeum, ILF, PP",

author = "Fenton, \{Thomas M.\} and J{\o}rgensen, \{Peter B.\} and Kristoffer Niss and Rubin, \{Samuel J.S.\} and M{\"o}rbe, \{Urs M.\} and Riis, \{Lene B.\} and \{Da Silva\}, Cl{\'e}ment and Adam Plumb and Julien Vandamme and Jakobsen, \{Henrik L.\} and S{\o}ren Brunak and Aida Habtezion and Nielsen, \{Ole H.\} and Bengt Johansson-Lindbom and Agace, \{William W.\}",

year = "2020",

month = mar,

day = "17",

doi = "10.1016/j.immuni.2020.02.001",

language = "English",

volume = "52",

pages = "557--570",

journal = "Immunity",

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Fenton, TM, Jørgensen, PB, Niss, K, Rubin, SJS, Mörbe, UM, Riis, LB, Da Silva, C, Plumb, A, Vandamme, J, Jakobsen, HL, Brunak, S, Habtezion, A, Nielsen, OH, Johansson-Lindbom, B & Agace, WW 2020, 'Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity', Immunity, vol. 52, no. 3, pp. 557-570. https://doi.org/10.1016/j.immuni.2020.02.001

TY - JOUR

T1 - Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity

AU - Fenton, Thomas M.

AU - Jørgensen, Peter B.

AU - Niss, Kristoffer

AU - Rubin, Samuel J.S.

AU - Mörbe, Urs M.

AU - Riis, Lene B.

AU - Da Silva, Clément

AU - Plumb, Adam

AU - Vandamme, Julien

AU - Jakobsen, Henrik L.

AU - Brunak, Søren

AU - Habtezion, Aida

AU - Nielsen, Ole H.

AU - Johansson-Lindbom, Bengt

AU - Agace, William W.

PY - 2020/3/17

Y1 - 2020/3/17

N2 - 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.

AB - 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.

KW - colon

KW - human intestinal regional mucosal follicles

KW - IgA

KW - iIeum

KW - ILF

KW - PP

UR - https://www.scopus.com/pages/publications/85081279962

U2 - 10.1016/j.immuni.2020.02.001

DO - 10.1016/j.immuni.2020.02.001

M3 - Article

C2 - 32160523

AN - SCOPUS:85081279962

SN - 1074-7613

VL - 52

SP - 557

EP - 570

JO - Immunity

JF - Immunity

IS - 3

ER -

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

Abstract

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