What is it about?

The study investigates the role of regulatory T cells (Treg) in controlling the metabolic status of CD4+ T cells in human prediabetes. The findings suggest that Treg control CD4+ T cell cytokine profiles differently in prediabetes compared to type 2 diabetes, and that Treg CD36 uniquely promotes Th17 cytokine production by Teff in prediabetes. The study concludes that nonlinear changes in T cell function during disease development culminate in the systemic Th17 profile of type 2 diabetes. The findings fundamentally differ from previous demonstrations of slow, steady increases in single inflammatory markers, and provide new targets for reversing prediabetes. [Some of the content on this page has been created by AI]

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Why is it important?

This research is important because it sheds light on the unique inflammatory state of human prediabetes, which remains largely nonactionable beyond advice for diet and exercise. The work provides new insights into the regulation of inflammation in prediabetes and type 2 diabetes, highlighting the role of Treg in controlling CD4+ T cell cytokine profiles through mechanisms determined by host metabolic status. The findings suggest new targets for reversing prediabetes, complementing existing recommendations for glycemic control and body weight management. Key Takeaways: 1. CD4+ T cell inflammation in subjects with prediabetes differs from that of lean subjects or subjects with type 2 diabetes, largely due to the Teff subset, which is regulated by CD36 on Treg. 2. Treg control Teff mitochondrial respiration from subjects with obesity, introducing a previously unappreciated mechanism of Treg action. 3. The lack of disease-associated differences in mRNAs that encode mitochondrial mediators of T cells suggests that complementary tools like metabolomics will be needed to identify mechanisms that Treg use to alter Teff mitochondrial function.


The finding that regulatory T cells (Treg) control effector T cell (Teff) function by altering Teff metabolism is fundamentally new. Exploring this concept in prediabetes and implicating Treg CD36 in this process applied our foundational discovery to mechanisms driving chronic inflammation in metabolic disease in people.

Barbara Nikolajczyk
University of Kentucky

Read the Original

This page is a summary of: Regulatory T cells control Effector T cell Inflammation in Human Prediabetes, Diabetes, November 2021, American Diabetes Association,
DOI: 10.2337/db21-0659.
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