Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and
promote TNFa production.
Authors Ip B, Cilfone NA, Belkina AC, DeFuria J, Jagannathan-Bogdan M, Zhu M,
Kuchibhatla R, McDonnell ME, Xiao Q, Kepler TB, Apovian CM, Lauffenburger DA,
Nikolajczyk BS
Submitted By Barbara Nikolajczyk on 11/30/2015
Status Published
Journal Obesity (Silver Spring, Md.)
Year 2015
Date Published 11/1/2015
Volume : Pages Not Specified : Not Specified
PubMed Reference 26576827
Abstract T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes
(T2DM). The identification of dominant sources of T cell inflammation in humans
remains a significant gap in understanding disease pathogenesis. It was
hypothesized that cytokine profiles from circulating T cells identify T cell
subsets and T cell cytokines that define T2DM-associated inflammation.,
Multiplex analyses were used to quantify T cell-associated cytokines in
aCD3/aCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM
or BMI-matched controls. Cytokine measurements were subjected to multivariate
(principal component and partial least squares) analyses. Flow cytometry
detected intracellular TNFa in multiple immune cell subsets in the
presence/absence of antibodies that neutralize T cell cytokines., T cell
cytokines were generally higher in T2DM samples, but Th17 cytokines are
specifically important for classifying individuals correctly as T2DM.
Multivariate analyses indicated that B cells support Th17 inflammation in T2DM
but not control samples, while monocytes supported Th17 inflammation regardless
of T2DM status. Partial least squares regression analysis indicated that both
Th17 and Th1 cytokines impact %HbA1c., Among various T cell subsets, Th17 cells
are major contributors to inflammation and hyperglycemia and are uniquely
supported by B cells in obesity-associated T2DM.

Complications