Joyce de Paula Souza, Justus S Fischer, Karine Jeanneau, Cyril Allard, Eline Angevaare, Dominik Aschenbrenner, Ursula Bodendorf, Benjamin Demarco, John S Gounarides, Saskia Killmer, Jiri Kovarik, Sabina Pfister, Hong Yin, Vithushan Ratnarasa, Marianne Bo Ni-Schnetzler, Matthias Hepprich, Daniel T Meier, Grazyna Wieczorek, Marc Y Donath
{"title":"2型糖尿病患者的血液特征及其外周血单个核细胞对nlrp3炎性体和caspase-1抑制剂的反应","authors":"Joyce de Paula Souza, Justus S Fischer, Karine Jeanneau, Cyril Allard, Eline Angevaare, Dominik Aschenbrenner, Ursula Bodendorf, Benjamin Demarco, John S Gounarides, Saskia Killmer, Jiri Kovarik, Sabina Pfister, Hong Yin, Vithushan Ratnarasa, Marianne Bo Ni-Schnetzler, Matthias Hepprich, Daniel T Meier, Grazyna Wieczorek, Marc Y Donath","doi":"10.1016/j.jcjd.2025.06.008","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":93918,"journal":{"name":"Canadian journal of diabetes","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blood characteristics of patients with type 2 diabetes and response of their peripheral blood mononuclear cells to inhibitors of the NLRP3-inflammasome and caspase-1.\",\"authors\":\"Joyce de Paula Souza, Justus S Fischer, Karine Jeanneau, Cyril Allard, Eline Angevaare, Dominik Aschenbrenner, Ursula Bodendorf, Benjamin Demarco, John S Gounarides, Saskia Killmer, Jiri Kovarik, Sabina Pfister, Hong Yin, Vithushan Ratnarasa, Marianne Bo Ni-Schnetzler, Matthias Hepprich, Daniel T Meier, Grazyna Wieczorek, Marc Y Donath\",\"doi\":\"10.1016/j.jcjd.2025.06.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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Blood characteristics of patients with type 2 diabetes and response of their peripheral blood mononuclear cells to inhibitors of the NLRP3-inflammasome and caspase-1.
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.