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Immune and non-immune functions of adipose tissue leukocytes

Nature Reviews Immunology volume 22, pages 371–386 (2022)Cite this article

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Abstract

Adipose tissue is a complex dynamic organ with whole-body immunometabolic influence. Much of the work into understanding the role of immune cells in adipose tissue has been in the context of obesity. These investigations have also uncovered a range of typical (immune) and non-typical functions exerted by adipose tissue leukocytes. Here we provide an overview of the adipose tissue immune system, including its role as an immune reservoir in the whole-body response to infection and as a site of parasitic and viral infections. We also describe the functional roles of specialized immunological structures found within adipose tissue. However, our main focus is on the recently discovered ‘non-immune’ functions of adipose tissue immune cells, which include the regulation of adipocyte homeostasis, as well as responses to changing nutrient status and body temperature. In doing so, we outline the therapeutic potential of the adipose tissue immune system in health and disease.

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Fig. 1: Fat-associated lymphoid structures.
Fig. 2: Adipose tissue macrophage populations.
Fig. 3: Immunological regulation of adipocyte homeostasis.
Fig. 4: Immunological control of adipocyte browning and thermogenesis.
Fig. 5: An overview of adipose tissue distribution between mice and humans.

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Acknowledgements

This work was supported by NIH grant R01 AI134861, ERC Starting Grant (679173), SFI FRL3865 and an American Diabetes Association grant (1-16-JDF-061).

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  1. School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland

    W. V. Trim & L. Lynch

  2. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    W. V. Trim & L. Lynch

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Glossary

Parabiotic

The surgical attachment of two living organisms (mice) that allows the connection of circulatory systems.

Innate-like B cell

An unconventional B cell that responds to innate signals such as Toll-like receptor agonists and microbial pathogens. Innate-like B cells produce regulatory cytokines (for example, IL-10) and large amounts of natural antibodies (primarily IgM) in the steady state, and provide early responses to infectious challenges.

Crowning macrophages

Large clusters of macrophages that coalesce around dead or dying adipocytes to facilitate the clearance and sequestration of cellular debris and lipids.

Matrix-induced neogenesis

The process by which, in the case of adipose tissue, macrophages interact with the extracellular matrix proteins that facilitate the recruitment, proliferation and differentiation of adipocyte progenitor cells, thereby leading to adipose tissue remodelling and adipogenesis.

Adipocyte browning and thermogenesis

Adipocyte browning is the adaptive process white adipocytes undergo in response to often environmentally derived signals such as cold exposure whereupon they increase their rate of mitochondrial biogenesis and mitochondrial respiration. Adipocyte thermogenesis is driven by the uncoupling of oxidative metabolism from ATP production, resulting in proton leakage across the mitochondrial inner membrane, eventually leading to heat production.

NLRP3 inflammasome

A multimeric protein complex that acts as an intracellular sensor for a wide-range of environmental and endogenous danger signals. Activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome initiates inflammation-induced cell death and triggers the release of IL-1β and IL-18.

Ketogenic diet

A high-fat, low-carbohydrate diet that drives a reliance on fats over carbohydrates for whole-body energetic needs. The resultant lack of available carbohydrates brings about the biochemical production of ketone bodies from fatty acids by the liver, inducing a metabolic state called ‘ketosis’.

Vγ6+δ1+ T cells

A subpopulation of γδ T cells characterized by their distinct T cell receptor γ and δ variable chains that specifically home (by an unknown mechanism) to, among other sites, adipose tissue.

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Trim, W.V., Lynch, L. Immune and non-immune functions of adipose tissue leukocytes. Nat Rev Immunol 22, 371–386 (2022). https://doi.org/10.1038/s41577-021-00635-7

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