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State of the union between metabolism and the immune system in type 2 diabetes

Genes & Immunity volume 12, pages 239–250 (2011)Cite this article

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Abstract

Lymphocytes and myeloid cells (monocyte/macrophages) have important roles in multiple types of diseases characterized by unresolved inflammation. The relatively recent appreciation of obesity, insulin resistance and type 2 diabetes (T2D) as chronic inflammatory diseases has stimulated interest in understanding the role of immune cells in metabolic imbalance. Myeloid cells regulate inflammation through cytokine production and the adipose tissue remodeling that accompanies hyper-nutrition, thus are critical players in metabolic homeostasis. More recently, multiple studies have indicated a role for T cells in obesity-associated inflammation and insulin resistance in model organisms, with parallel work indicating that pro-inflammatory changes in T cells also associate with human T2D. Furthermore, the expansion of T cells with similar antigen-binding sites in obesity and T2D indicates these diseases share characteristics previously attributed to inflammatory autoimmune disorders. Parallel pro-inflammatory changes in the B-cell compartment of T2D patients have also been identified. Taken together, these studies indicate that in addition to accepted pro-inflammatory roles of myeloid cells in T2D, pro-inflammatory skewing of both major lymphocyte subsets has an important role in T2D disease pathogenesis. Basic immunological principles suggest that alterations in lymphocyte function in obesity and T2D patients are an integral part of a feed-forward pro-inflammatory loop involving additional cell types. Importantly, the pro-inflammatory loop almost inevitably includes adipocytes, known to respond to pro-inflammatory, pro-diabetogenic cytokines originating from the myeloid and lymphoid compartments. We propose a model for inflammation in T2D that functionally links lymphocyte, myeloid and adipocyte contributions, and importantly proposes that tools for B-cell ablation or regulation of T-cell subset balance may have a place in the endocrinologist's limited arsenal.

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Acknowledgements

This work was supported by NIH R01 AI54611, NIH R21 DK089270 and a Research Grant from the American Diabetes Association. The authors thank Susan Fried, Gerald Denis, Jongsoon Lee, Marty Obin, and Marie McDonnell for valuable conversations related to this work.

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Authors and Affiliations

  1. Departments of Microbiology and Medicine, Boston University School of Medicine, Boston, MA, USA

    B S Nikolajczyk & H Shin

  2. Department of Pathology, Boston University School of Medicine, Boston, MA, USA

    M Jagannathan-Bogdan

  3. Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Boston, MA, USA

    R Gyurko

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  1. B S Nikolajczyk
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  2. M Jagannathan-Bogdan
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  3. H Shin
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Correspondence to B S Nikolajczyk.

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Nikolajczyk, B., Jagannathan-Bogdan, M., Shin, H. et al. State of the union between metabolism and the immune system in type 2 diabetes. Genes Immun 12, 239–250 (2011). https://doi.org/10.1038/gene.2011.14

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  • DOI: https://doi.org/10.1038/gene.2011.14

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