de Paula Souza, Joyce, Jeanneau, Karine, Allard, Cyril, Angevaare, Eline, Aschenbrenner, Dominik, Bassi, Zuni, Bodendorf, Ursula, Demarco, Benjamin, Farady, Christopher, Gounarides, John, Killmer, Saskia, Kovarik, Jiri, Pfister, Sabina, Yin, Hong2, Hepprich, Matthias, Fischer, Justus S., Ratnarasa, Vithushan, Böni-Schnetzler, Marianne, Meier, Daniel T., Wieczorek, Grazyna and Donath, Marc Y. (2025) Blood characteristics of adults with type 2 diabetes and response of their peripheral blood mononuclear cells to inhibitors of the NLRP3-inflammasome and caspase-1. Canadian journal of diabetes.. ISSN 2352-3840; 1499-2671

Abstract

Obesity and aging are associated with increased activity of the innate immune system. This chronic systemic inflammation contributes to the development of type 2 diabetes and long-term complications and is partly driven by the activation of the NLRP3 inflammasome. We conducted a comparative analysis of clinical parameters, non-esterified fatty acid (NEFA) profiles, immune cell subsets, and inflammatory responses of peripheral blood mononuclear cells obtained from both healthy individuals and those diagnosed with type 2 diabetes. Plasma NEFA profiling revealed a dysregulation in patients with type 2 diabetes, indicating potential modulation of immune cell responses by lipids, along with leukocytosis, elevated serum levels of inflammatory cytokines, the inflammasome-related protein ASC, IL-1RA, and IL-18BPa. Surprisingly, functional assessments demonstrated comparable NLRP3 inflammasome activity in peripheral blood mononuclear cells (PBMCs) from both groups, suggesting that systemic inflammation in type 2 diabetes is driven by elevated leucocyte numbers or resident tissue macrophages. Treatment of PBMCs with NLRP3 and caspase-1 inhibitors attenuated the release of pro-inflammatory cytokines ex vivo. Therefore, inhibition of inflammasome activation emerges as a promising therapeutic strategy for management of diabetes-related complications.

Item Type:	Article
Keywords:	NLRP3, CASP-1, NEK-7, IL-1b, IL-18, T2D
Date Deposited:	12 Aug 2025 00:45
Last Modified:	12 Aug 2025 00:45
URI:	https://oak.novartis.com/id/eprint/55339