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Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria

Nature Reviews Immunology volume 10, pages 415–426 (2010)Cite this article

Subjects

Key Points

  • Mononuclear phagocytes are essential for the maintenance of intestinal homeostasis and have crucial roles in inflammatory bowel diseases (IBDs), both in mouse and man. The maintenance of robust gut homeostasis requires the presence of two mononuclear phagocyte populations of distinct origin and function.

  • CD11b+CD103+ dendritic cells (DCs) are poised to migrate to the draining mesenteric lymph nodes to initiate and modulate primary T cell immune responses.

  • CX3C-chemokine receptor 1 (CX3CR1)+ mononuclear phagocytes (which have also been termed DCs) do not migrate to the mesenteric lymph nodes but function locally in the mucosa and may maintain effector and regulatory T cells.

  • Mouse research requires a better understanding of mononuclear phagocytes during disease, but in humans we lack fundamental insights into the steady state functions of these cells.

  • For research into IBDs to capitalize on the progress made with small animal models, it will be important to align human and mouse mononuclear phagocyte populations.

Abstract

The intestinal landscape comprises the host's own tissue and immune cells, as well as a diverse intestinal microbiota. Intricate regulatory mechanisms have evolved to maintain peaceful coexistence at this site, the breakdown of which can result in devastating inflammatory bowel diseases (IBDs). Mononuclear phagocytes promote both innate and adaptive immune responses in the gut and, as such, are essential for the maintenance of intestinal homeostasis. Here, we review the origins and functions of the mononuclear phagocytes found in the intestinal lamina propria, highlighting the problems that have arisen from their classification. Understanding these cells in their physiological context will be important for developing new therapies for IBDs.

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Figure 1: Imaging intestinal CX3 CR1+ lamina propria mononuclear phagocytes.
Figure 2: The emerging intestinal lamina propria dendritic cell compartment.

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Acknowledgements

This work was supported by the Israel Science Foundation, The Thyssen Foundation and a research grant from the estate of Edith F. Goldensohn Center (S.J.).

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  1. Gastroenterology and Hepatology Institute, Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel

    Chen Varol & Ehud Zigmond

  2. Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel

    Ehud Zigmond & Steffen Jung

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  1. Chen Varol
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  2. Ehud Zigmond
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  3. Steffen Jung
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Correspondence to Steffen Jung.

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Glossary

Peyer's patches

Groups of lymphoid nodules present in the small intestine. They occur massed together on the intestinal wall, opposite the line of attachment of the mesentery. Peyer's patches consist of a dome area, B cell follicles and interfollicular T cell areas.

Isolated lymphoid follicles

Dynamic aggregates of lymphoid cells found in the mouse small intestinal lamina propria; similar lymphoid aggregates have also been identified in the mouse colon. Isolated lymphoid follicles have germinal centres and an overlying follicle-associated epithelium containing microfold (M) cells specialized for antigen uptake, but they lack discrete T cell zones. They are formed de novo in adult animals in response to commensal organism-derived stimuli and, although their function is not completely clear, they may be inductive sites of immunity in the intestinal lamina propria.

Bromodeoxyuridine

A thymidine analogue that can be incorporated into DNA during DNA replication. Treatment with bromodeoxyuridine enables the detection of cells that are dividing or have recently divided.

Ly6Chi monocytes

A subset of blood monocytes that is derived from MDPs in the bone marrow and emigrates in a CCR2-dependent way to the blood. Ly6Chi monocytes can home back to the bone marrow in the steady state and differentiate into Ly6Clow monocytes. Following pathogen challenge, Ly6Chi monocytes can give rise to splenic TIP-DCs. Furthermore they are the precursors of CX3CR1+ mononuclear phagocytes in the intestinal lamina propria. In addition, Ly6Chi monocytes can contribute to tissue remodelling and healing processes.

Crypts of Lieberkuhn

Tubular invaginations of the intestinal epithelium. Paneth cells are found at the base of the crypts along with continuously dividing stem cells, which are the source of all intestinal epithelial cells.

Metagenome

The genomic content of a sample of organisms obtained from a common habitat.

Gnotobiotic mice

Mice that are born in aseptic conditions, separated from the mother by Caesarean section, and are raised in controlled environment. These animals can be monocolonized with defined microbial species in order to investigate specific relationships between the host and the microbiota.

Genome wide association (GWA) studies

An approach that involves rapidly scanning single nucleotide polymorphism markers across the complete genomes of many individuals to find genetic variations associated with a particular disease.

SLAN

(6-Sulfo LacNAc). A carbohydrate modification of the P-selectin glycoprotein 1 (PSGL1). SLAN is expressed by a subset of DCs found in human blood and is recognized by the monoclonal antibody MDC8.

Autophagy

Any process involving degradative delivery of a portion of the cytoplasm to the lysosome that does not involve direct transport through the endocytic or vacuolar protein sorting pathways.

Paneth cells

Paneth cells are found at the base of intestinal crypts and produce antimicrobial proteins and peptides, including phospholipase A2 and defensins.

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Varol, C., Zigmond, E. & Jung, S. Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria. Nat Rev Immunol 10, 415–426 (2010). https://doi.org/10.1038/nri2778

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