Fat-loving Tregs control insulin sensitivity during ageing

I have noticed in the past couple of weeks that there is a surge of Foxp3⁺ T cell papers published in top journals. Just yesterday Nature published another paper where the authors claim that they have discovered ageing-related [separate] pathway of insulin resistance driven by fat-associated Tregs.

Lets review their claims. First, the authors showed that unlike "classical" obesity-driven insulin resistance, ageing-related insulin resistance is characterized by enrichment of Foxp3⁺ T cells in adipose tissue (visceral adipose tissue, VAT).

Next, the authors showed that selective depletion of fat Tregs in ageing Foxp3^cre PPARγ ^fl/fl mice promoted shift into "lean body" metabolism[selective decrease in fat mass].

This shift to lean body metabolism in fat Treg depleted mice [i.e. insulin sensitivity ↑] occurred in ageing mice, not in young or obese mice.

Finally, since most of fat Tregs were positive for surface ST2, a receptor for IL-33, their depletion in ageing mice with anti-ST2 antibody [not very efficient by the way] could still improve insulin sensitivity by 25% over control [without any overt inflammation].

In summary, this study uncovered a novel pathway of ageing-associated insulin resistance driven by ST2⁺ fat Tregs. This pathway differs from obesity-driven insulin resistance. However, it is important to remember here that B6 mice [used in this experiments] have strong tendency for obesity during ageing and it remains seen whether this phenomenon with fat Tregs will be applicable for other strains or for humans.

David Usharauli