1) Objectives To establish adaptive immune cells specifically T helpers as mediators of meta-inflammation in Type 2 Diabetes Mellitus, correlate biochemical and immunological parameters and delineate the specific signaling proteins responsible for it. 2) Research Design and Methods 100 T2DM patients with no other clinical disease, autoimmunity or infection were recruited and analyzed for their biochemical and immune parameters. Bioplexing and flow cytometry was employed to analyse total and cell specific protein secretion respectively. Ex-vivo inhibition studies were performed using targeted monoclonal antibodies or small molecule STAT inhibitors. 3) Results CD4+ T-cells were found to be the primary source for meta-inflammation in T2DM patients with multiple pro-inflammatory cytokines and antibody isotypes. TNF-a acting through STAT-3 was shown as the primary pathway implicating meta-inflammation through CD4+ T-cells, wherein inhibitor studies revealed subtle pathways differences between TNF-a or STAT-3 inhibition. 4) Conclusions Our result suggests that chronic meta-inflammation with a dysregulated biochemical profile have severe implications on immune function. Additionally, TNF-a and STAT-3 inhibition are good therapeutic targets for better T2MD treatment in ameliorating meta-inflammation.

The authors have declared no competing interest.

This study was supported by the core funding of iBRIC-Institute of Life Sciences, Bhubaneswar, Department of Biotechnology (DBT), Government of India

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Ethics Committee/HEC of Institute of Life sciences gave ethical approval of this work (HEC Ref No: 35/HEC/14)

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