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Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes

Open access
Jagannathan-Bogdan, Madhumita, McDonnell, Marie E, Shin, Hyunjin, Rehman, Qasim, Hasturk, Hatice, Apovian, Caroline M, Nikolajczyk, Barbara S·2011·The Journal of Immunology

Abstract

An appropriate balance between proinflammatory (Th17 and Th1) and anti-inflammatory (regulatory T cells [Tregs] and Th2) subsets of T cells is critical to maintain homeostasis and avoid inflammatory disease. Type 2 diabetes (T2D) is a chronic inflammatory disease promoted by changes in immune cell function. Recent work indicates T cells are important mediators of inflammation in a mouse model of T2D. These studies identified an elevation in the Th17 and Th1 subsets with a decrease in the Treg subset, which culminates in inflammation and insulin resistance. Based on these data, we tested the hypothesis that T cells in T2D patients are skewed toward proinflammatory subsets. Our data show that blood from T2D patients has increased circulating Th17 cells and elevated activation of Th17 signature genes. Importantly, T cells required culture with monocytes to maintain Th17 signatures, and fresh ex vivo T cells from T2D patients appeared to be poised for IL-17 production. T cells from T2D patients also have increased production of IFN-γ, but produce healthy levels of IL-4. In contrast, T2D patients had decreased percentages of CD4+ Tregs. These data indicate that T cells in T2D patients are naturally skewed toward proinflammatory subsets that likely promote chronic inflammation in T2D through elevated cytokine production. Potential therapies targeted toward resetting this balance need to be approached with caution due to the reciprocal relationship between Th17 cells and Tregs. Understanding the unique aspects of T2D T cells is essential to predict outcomes of such treatments.

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Metadata

Authors
Jagannathan-Bogdan, M., McDonnell, M. E., Shin, H., Rehman, Q., Hasturk, H., Apovian, C. M., & Nikolajczyk, B. S.
Venue
The Journal of Immunology
Published
2011-01
Volume
186
Issue
2
Pages
1162-1172
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2167619945
Cited by
417
References
68
FWCI
6.67
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes. https://app.cochat.ai/papers/10.4049/jimmunol.1002615
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Jagannathan-Bogdan, M., McDonnell, M. E., Shin, H., Rehman, Q., Hasturk, H., Apovian, C. M., & Nikolajczyk, B. S. (2011). Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1002615

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