The aberrant expression of CD69 on peripheral T-helper cells in diet-induced inflammation is ameliorated by low-dose aspirin and metformin treatment

Cell Immunol. 2021 May:363:104313. doi: 10.1016/j.cellimm.2021.104313. Epub 2021 Feb 13.

Abstract

Chronic inflammation in patients with type 2 diabetes (T2D) is associated with T-cell dysfunction. Using a rodent model, we evaluated changes in metabolic profiles, inflammation status and the expression of T-cell function markers following high-fat diet (HFD)-feeding. In addition, we assessed the modulatory effects of treatment with low-dose aspirin (LDA) and its combination with metformin (LDA + Met) on these parameters. Notably, HFD-feeding induced metabolic disorders and aggravated inflammation. Most importantly, it was associated with decreased expression of CD69 on T-helper cells but had no effect on the expression of programmed cell death 1 (PD-1). Treatment with LDA monotherapy had no effect on metabolic profiles. However, its combination with metformin ameliorated the levels of inflammation and up-regulated the expression of CD69 although it had no therapeutic effect on the levels of PD-1 expression. Therefore, alleviating inflammation and lowering glucose levels in T2D may be an effective strategy to improve T-cell function in these patients.

Keywords: CD69; Inflammation; Low-dose aspirin; Metformin; PD-1; T-cell regulation; Type 2 diabetes mellitus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Aspirin / pharmacology*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diet, High-Fat
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Hypoglycemic Agents / therapeutic use
  • Inflammation / immunology
  • Lectins, C-Type / immunology*
  • Male
  • Metformin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Blood Glucose
  • CD69 antigen
  • Hypoglycemic Agents
  • Lectins, C-Type
  • Metformin
  • Aspirin