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Research_ArticleResearch Article

Hyperglycemia Activates the CD27-CD70 Axis on Human Peripheral Blood Mononuclear Cells

Claire Owaja, Evelyn Roback-Navarro, Naomi Iwai and Nadine Lerret
American Society for Clinical Laboratory Science January 2020, ascls.119.002089; DOI: https://doi.org/10.29074/ascls.119.002089
Claire Owaja
1 Rush University;
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Evelyn Roback-Navarro
2 Rush University Medical Center
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Naomi Iwai
2 Rush University Medical Center
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Nadine Lerret
2 Rush University Medical Center
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  1. Claire Owaja1
  2. Evelyn Roback-Navarro2
  3. Naomi Iwai2
  4. Nadine Lerret2,3
  1. 1 Rush University;
  2. 2 Rush University Medical Center
  1. ↵* Corresponding author; email: nadine_lerret{at}rush.edu

Abstract

Obesity is now strongly associated with chronic low-grade inflammation that, without intervention, contributes to the development of pre-diabetes and eventually Type 2 diabetes. While the exact mechanism that inflammation plays in the pathogenesis from obesity to Type 2 diabetes is unclear, activated immune cells and pro-inflammatory cytokines have been found in the adipose tissue of Type 2 diabetics, implicating their role in the disease process. The CD27-CD70 pathway provides a crucial inflammatory co-stimulatory signal, with CD70 being expressed on activated antigen presenting cells, and CD27 expressed on lymphocytes. While the CD27-CD70 axis is being explored in other models of chronic inflammation, such as rheumatoid arthritis and colitis, the role played in Type 2 diabetes remains unknown. Here we report the downregulation of CD27 on CD4 T cells when co-cultured with dendritic cells primed in increasing concentrations of glucose, indicating an effector phenotype of these T cells. Importantly, we also highlight that CD70 is concurrently upregulated on dendritic cells primed in high concentrations of glucose, resulting in increased production of IFN-γ and TNF-α by the CD70 expressing dendritic cells, when compared to dendritic cells primed in a lower concentration of glucose. These results reveal a novel role for CD27-CD70 interactions in the pathogenesis of Type 2 diabetes and provide support for future investigations into this pathway. Additionally, CD27 could be analyzed as a way to further stratify pre-diabetic patients and guide diagnosticians towards the most efficient therapy.

  • Chemistry
  • CD4-Positive T-lymphocytes
  • Dendritic cell
  • Diabetes Mellitus, Type 2
  • Received September 4, 2019.
  • Revision received December 12, 2019.
  • Accepted December 14, 2019.
  • Published by American Society for Clinical Laboratory Science
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American Society for Clinical Laboratory Science: 30 (4)
American Society for Clinical Laboratory Science
Vol. 30, Issue 4
Fall 2017
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Hyperglycemia Activates the CD27-CD70 Axis on Human Peripheral Blood Mononuclear Cells
Claire Owaja, Evelyn Roback-Navarro, Naomi Iwai, Nadine Lerret
American Society for Clinical Laboratory Science Jan 2020, ascls.119.002089; DOI: 10.29074/ascls.119.002089

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Hyperglycemia Activates the CD27-CD70 Axis on Human Peripheral Blood Mononuclear Cells
Claire Owaja, Evelyn Roback-Navarro, Naomi Iwai, Nadine Lerret
American Society for Clinical Laboratory Science Jan 2020, ascls.119.002089; DOI: 10.29074/ascls.119.002089
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Keywords

  • Chemistry
  • CD4-Positive T-lymphocytes
  • Dendritic cell
  • Diabetes Mellitus, Type 2

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