Emergence of T cell immunosenescence in diabetic chronic kidney disease

Abstract

Background Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. Method 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. Result Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. Conclusion The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

“…Various indications of immunological dysfunction, leading to infectious complications [ 33 ], including accelerated aging of the thymus and other lymphoid organs and insufficient adaptive immune response [ 34 , 35 ], characterize uremia at the systemic level. An increase in systemic proinflammatory processes is also a hallmark of this disorder, which is linked to premature body aging [ 36 ].…”

Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis

“…Researchers confirmed that CD153 and CD30 signaling may interact with CD153 + PD-1 + CD4 + senescence-associated T cells (SAT) and CD30 + T-bet + age-related B cells, resulting in tertiary lymphoid tissue generation in chronically inflammatory organs, thereby promoting renal inflammation and fibrosis ( 173 ). In addition to ESRD, CD8 + T cell depletion occurs as early as CKD3 in diabetes mellitus, showing the characteristics of aggravated immunosenescence ( 174 ). Moreover, the occurrence and development of kidney diseases might be associated with cardiovascular diseases.…”

Immune Response to SARS-CoV-2 Infection in Obesity and T2D: Literature Review

“…Overall, the activation of intracellular pathways accompanied by adipose inflammation increases the production of pro-inflammatory cytokines and promotes the infiltration of more pro-inflammatory M1 macrophages. Additionally, a hallmark in obesity and T2D are the senescent immune cells which exhibit a senescence-associated secretory phenotype (SASP) characterized by secreting a huge quantity of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-18, CCL-2, and TNF-α) [ 80 , 81 , 82 ]. SASP cells have enhanced mitochondrial apoptosis switching from apoptosis to pyroptosis, through a high mitogen-activated protein kinases (MAPKs) activity which drive IL-1 production (leading to auto-inflammation) and reduced IFN type 1 production, leading to a deficiency to combat viral infections [ 83 ] (see Figure 1 ).…”