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,...
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doaj-97d98558dca54af4b5ba0935e5f547202020-11-25T03:05:39ZengBMCImmunity & Ageing1742-49332020-10-0117111010.1186/s12979-020-00200-1Emergence of T cell immunosenescence in diabetic chronic kidney diseaseYen-Ling Chiu0Wan-Chuan Tsai1Ruo-Wei Hung2I-Yu Chen3Kai-Hsiang Shu4Szu-Yu Pan5Feng-Jung Yang6Te-Tien Ting7Ju-Ying Jiang8Yu-Sen Peng9Yi-Fang Chuang10Graduate Program in Biomedical Informatics, Department of Computer Science and Engineering, College of Informatics, Yuan Ze UniversityDivision of Nephrology, Department of Medicine, Far Eastern Memorial HospitalDivision of Nephrology, Department of Medicine, Far Eastern Memorial HospitalDivision of Nephrology, Department of Medicine, Far Eastern Memorial HospitalDivision of Nephrology, Department of Medicine, Far Eastern Memorial HospitalDivision of Nephrology, Department of Medicine, Far Eastern Memorial HospitalDepartment of Medicine, National Taiwan University Hospital Yun Lin BranchSchool of Big Data Management, Soochow UniversityDivision of Endocrinology and Metabolism, Department of Medicine, Far Eastern Memorial HospitalDivision of Nephrology, Department of Medicine, Far Eastern Memorial HospitalInstitute of Public Health, School of Medicine, National Yang-Ming UniversityAbstract 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.http://link.springer.com/article/10.1186/s12979-020-00200-1ImmunosenescenceCKDT cellDiabetesBMI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yen-Ling Chiu Wan-Chuan Tsai Ruo-Wei Hung I-Yu Chen Kai-Hsiang Shu Szu-Yu Pan Feng-Jung Yang Te-Tien Ting Ju-Ying Jiang Yu-Sen Peng Yi-Fang Chuang |
spellingShingle |
Yen-Ling Chiu Wan-Chuan Tsai Ruo-Wei Hung I-Yu Chen Kai-Hsiang Shu Szu-Yu Pan Feng-Jung Yang Te-Tien Ting Ju-Ying Jiang Yu-Sen Peng Yi-Fang Chuang Emergence of T cell immunosenescence in diabetic chronic kidney disease Immunity & Ageing Immunosenescence CKD T cell Diabetes BMI |
author_facet |
Yen-Ling Chiu Wan-Chuan Tsai Ruo-Wei Hung I-Yu Chen Kai-Hsiang Shu Szu-Yu Pan Feng-Jung Yang Te-Tien Ting Ju-Ying Jiang Yu-Sen Peng Yi-Fang Chuang |
author_sort |
Yen-Ling Chiu |
title |
Emergence of T cell immunosenescence in diabetic chronic kidney disease |
title_short |
Emergence of T cell immunosenescence in diabetic chronic kidney disease |
title_full |
Emergence of T cell immunosenescence in diabetic chronic kidney disease |
title_fullStr |
Emergence of T cell immunosenescence in diabetic chronic kidney disease |
title_full_unstemmed |
Emergence of T cell immunosenescence in diabetic chronic kidney disease |
title_sort |
emergence of t cell immunosenescence in diabetic chronic kidney disease |
publisher |
BMC |
series |
Immunity & Ageing |
issn |
1742-4933 |
publishDate |
2020-10-01 |
description |
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. |
topic |
Immunosenescence CKD T cell Diabetes BMI |
url |
http://link.springer.com/article/10.1186/s12979-020-00200-1 |
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