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The influence of metabolic disorders on adaptive immunity

Abstract

The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis. Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired. There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired. In the context of metabolic disorders, chronic inflammation is suggested to be a major contributor to disease progression. A major contributor to tissue dysfunction in metabolic disease is ectopic lipid deposition, which is generally caused by diet and genetic factors. Thus, we propose the idea, that similar to tissue and organ damage in metabolic disorders, excessive accumulation of lipid in immune cells promotes a dysfunctional immune system (beyond the classical foam cell) and contributes to disease pathology. Herein, we review the evidence that lipid accumulation through diet can modulate the production and function of immune cells by altering cellular lipid content. This can impact immune cell signalling, activation, migration, and death, ultimately affecting key aspects of the immune system such as neutralising pathogens, antigen presentation, effector cell activation and resolving inflammation.

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Acknowledgements

We are grateful to the following funding sources: National Health and Medical Research Council of Australia grants GNT2027074 & GNT2012119 to KM, GNT1189012 to GIL and GNT1194329 to AJM.

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Collins, T.J.C., Morgan, P.K., Man, K. et al. The influence of metabolic disorders on adaptive immunity. Cell Mol Immunol 21, 1109–1119 (2024). https://doi.org/10.1038/s41423-024-01206-1

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