The alteration of Th1/Th2/Th17/Treg paradigm in patients with type 2 diabetes mellitus: Relationship with diabetic nephropathy

Hum Immunol. 2014 Apr;75(4):289-96. doi: 10.1016/j.humimm.2014.02.007. Epub 2014 Feb 12.


T cells have been demonstrated to exert central roles in the development of type 2 DN (T2DN). To explore whether Th1/Th2/Th17/Treg paradigm plays an important role in the development of T2DN, we investigated the proportions of Th1/Th2/Th17/Treg cells and serum levels of relevant cytokines in T2DM patients with various degrees of nephropathy and controls. Moreover, we analyzed the relationships between the Th1/Th2/Th17/Treg paradigm or relevant cytokines with urine albumin:creatinine ratio (UACR). Our study demonstrated that the Th1/Th2/Th17/Treg paradigm skewed to Th1 and Th17 in T2DN patients. UACR was positively related to the proportions of Th1 and Th17 cells, as well as the ratio of Th17:Treg cells, and negatively related to the proportions of Treg cells. Furthermore, serum levels of IL-6, IL-17, IFN-γ, TNF-α, IL-2 and IL-10 were increased in T2DN patients, and positively related to UACR. These data indicate that the alteration of Th1/Th2/Th17/Treg paradigm exists in T2DN patients, which may contribute to the enhanced immune activation and inflammation, and subsequent development and progression of T2DN. These findings may provide one new approach to the underlying mechanisms of the development of T2DN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria
  • Case-Control Studies
  • Creatinine / urine
  • Cytokines / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / etiology
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Risk Factors
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • Cytokines
  • Glycated Hemoglobin A
  • Creatinine