ICOS signaling in visceral adipose tissue regulatory T cell homeostasis and function

• Published in: The Journal of immunology (1950) 2019-05, Vol.202 (1_Supplement), p.128-128.4
• Main Authors: Mittelsteadt, Kristen L, Campbell, Daniel J.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.202.Supp.128.4

Obesity and insulin resistance/type 2 diabetes are linked by chronic inflammation in visceral adipose tissue (VAT). Foxp3+ regulatory T cells (TR) are critical for maintaining immune tolerance and are recently appreciated for their role in tissue repair and homeostasis. Indeed, a unique population of TR reside in the VAT of mice and humans, and these TR regulate adipose inflammation and preserve insulin sensitivity and glucose tolerance. ICOS is a costimulatory molecule expressed at high levels by TR. Surprisingly, the abundance of TR in VAT is elevated by nearly 2-fold in IcosKO mice compared to WT controls, and IcosKO TR preferentially reconstitute the VAT of WT:IcosKO mixed bone marrow chimeras. TR in the VAT of IcosKO mice express high levels of VAT-TR markers, like ST2, KLRG1, and IL-10, compared to WT mice, suggesting a potent ability to prevent insulin resistance and diet-induced metabolic syndrome. Ongoing studies aim to determine whether IcosKO mice are more resistant to diet-induced metabolic syndrome by assessing insulin sensitivity/glucose tolerance, indices of inflammation, and VAT immune cell phenotype and function, and to mechanistically elucidate how ICOS signaling controls the accumulation and phenotype of VAT-TR. These studies will yield important information on the molecular pathways involved in regulating the onset of metabolic syndrome and provide new potential therapeutic targets.