Role of Innate and Adaptive Immune Cells in the Metabolic Syndrome

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Background

Metabolic disorders, such as diabetes, obesity and cardiovascular diseases, represent a heterogeneous cluster of related diseases generally characterized by accumulation of surplus body fat, hypertension, increased levels of blood glucose, and abnormal lipid profile. Emerging studies in preclinical models and in human subjects have provided overwhelming evidence that these metabolic disorders are also invariably characterized by a state of chronic inflammation, termed “metaflammation”.

Dyslipidemia, hypercholesterolemia and hyperglycemia, are among the metabolic disturbances that can trigger immune cell activation, infiltration into tissues and contribute to pathology. While the lipid-rich and/or glucose-rich microenvironment prompts metabolic adaptations in immune cells, the infiltrates in turn produces a myriad of inflammatory mediators that alter metabolic functions such as lipolysis or lipogenesis, insulin sensitivity and glucose utilization in the surrounding tissues. Both innate and adaptive immune cells are involved in this crosstalk, directly affected in their functions by metabolic regulation, and thus contribute to disease pathogenesis by orchestrating local and systemic inflammation that recalibrates metabolic homeostasis.

Understanding the connection of metabolism and inflammation mechanistically on a cellular as well as organismal level is of great clinical interest. With a growing appreciation for the role of immune cells in driving metabolic diseases, interventions that curb inflammation are being explored as treatment options. Landmark clinical trials that tested the efficacy of IL-1β blockade in cardiovascular diseases or IL-1-R antagonism in type 2 diabetes, have provided encouraging evidences to support the feasibility of managing metabolic disorders by targeting inflammatory pathways. However, systemic immunosuppression may lead to adverse outcomes such as increased incidence of infections in the treated group. This was observed in the Canakinumab Anti- Inflammatory Thrombosis Outcome Study (CANTOS) trial. Precise targeting of metabolic inflammation will require a more comprehensive understanding of the cellular and molecular components involved in metaflammation. The goal of this research topic is to provide a platform to report and discuss latest discoveries that provide mechanistic clarification of the processes that promote immune cell activation and metabolic reprogramming, their functional implications and potential opportunities for immune-based interventions in diseases of the metabolic syndrome, with particular focus on obesity, diabetes and cardiovascular diseases.

We welcome submissions of Original Research Articles, Reviews/Mini Reviews, Opinion, Perspectives and other types of articles addressing these and related issues. Potential topics include, but are not limited to, the following:

- Chemical and biological triggers of immune cell infiltration and activation in metaflammation
- Pleiotropic effects of cytokines in impacting metabolic adaptations
- Signalling pathways and gene signatures defining dysregulated metabolic states
- Molecular mediators of metabolic crosstalk between immune and non-immune cells
- Novel therapeutic strategies that target immunometabolic imbalances

Keywords: immune cell response, cardiovascular disease, metainflammation, metabolic syndrome

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