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20231226083416.0 |
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231226s2023 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2023.109729
|2 doi
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|a pubmed24n1202.xml
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|a (DE-627)NLM360622968
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|a (NLM)37562723
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|a (PII)S1521-6616(23)00492-8
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Li, Zeying
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes
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|c 2023
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 02.10.2023
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|a Date Revised 02.10.2023
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2023 Elsevier Inc. All rights reserved.
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|a Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune system's failure to maintain self-tolerance, resulting in the autoimmune destruction of pancreatic beta cells. Although T1D has conventionally been viewed as a T-cell-dominant disease, recent research has emphasized the contribution of B cells in the onset of the disease. However, the mechanism underlying aberrant B cell responses remains unknown. B cell metabolism is a crucial prerequisite for B cell function and the development of adaptive immune responses. Here, we investigated the metabolic features of B cells, first in a cross-sectional cohort and subsequently in non-obese diabetic (NOD) mice, and revealed that there is an increased frequency of high-glucose-avidity (2-NBDGhigh) B cell population that may contribute to T1D progression. Further characterization of the metabolic, transcriptional and functional phenotype of B cells in NOD mice found that elevated glucose avidity is associated with a greater capacity for co-stimulation, proliferation and inflammatory cytokine production. Mechanistically, elevated Myc signaling orchestrated the glucose metabolism and the pro-inflammatory response of B cells in T1D. In vitro experiments demonstrated that pharmacological inhibition of glucose metabolism using metformin and 2-DG reduced pro-inflammatory cytokine production and B cell proliferation. Moreover, the combination of these inhibitors successfully delayed insulitis development, onset of diabetes, and improved high blood glucose levels in streptozotocin (STZ)-induced diabetic mice model. Taken together, our work has uncovered these high-glucose-avidity B cells as novel adjuvant diagnostic and therapeutic targets for T1D
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Autoimmunity
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|a B cells
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|a Glucose metabolism
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|a LADA
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|a Metabolic inhibitors
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| 650 |
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4 |
|a Type 1 diabetes
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| 650 |
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|a Proto-Oncogene Proteins c-myc
|2 NLM
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| 650 |
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|a Cytokines
|2 NLM
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| 650 |
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|a Glucose
|2 NLM
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| 650 |
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|a IY9XDZ35W2
|2 NLM
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| 700 |
1 |
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|a Zhao, Mingjiu
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Li, Jingyue
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Luo, Wenjun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Huang, Juan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Huang, Gan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Xie, Zhiguo
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Xiao, Yang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Huang, Jiaqi
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Li, Xia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhao, Bin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhou, Zhiguang
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 255(2023) vom: 01. Okt., Seite 109729
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
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|g volume:255
|g year:2023
|g day:01
|g month:10
|g pages:109729
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|u http://dx.doi.org/10.1016/j.clim.2023.109729
|3 Volltext
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