Non-obese Type 2 Diabetes Patients Present Intestinal B Cell Dysregulations Associated With Hyperactive Intestinal Tfh Cells

Mol Immunol. 2018 May;97:27-32. doi: 10.1016/j.molimm.2018.03.008. Epub 2018 Mar 16.

Abstract

Most current studies of type 2 diabetes (T2D) focus on obesity in the pathogenesis of the disease. However, many individuals develop T2D at non-obese body mass index (BMI) level. It is yet unclear whether certain etiological mechanisms discovered in these obese models can apply to non-obese T2D patients. In the present study, we focused on one aspect that was potentially involved in T2D development, the intestinal inflammation, and examined the difference between non-obese T2D patients and BMI-matched healthy controls. We found that non-obese T2D patients presented significantly higher levels of fecal IgG than BMI-matched controls. Compared to active Crohn's disease patients, both T2D and healthy controls presented lower levels of fecal IgG. In the mucosal biopsies, the B cells and plasmablasts from T2D patients presented a slight but significant increase in the frequencies of cells with surface IgG expression compared to those from healthy individuals. The potential mechanism resulting in increased IgG expression was then examined. The CD4+CXCR5+ T cells (Tfh) from non-obese T2D patients were highly enriched in IFN-γ-producing cells and depleted in IL-4- and IL-17-producing cells. Presence of mucosal CD4+CXCR5+ T cells significantly increased IgG production from mucosal samples. Interestingly, when stimulated with E. coli, a common intestinal microbe, the CD4+CXCR5+ T cells from T2D patients presented significantly higher IFN-γ expression than CD4+CXCR5+ T cells from BMI-matched controls Together, these results demonstrated that non-obese T2D patients presented a low-grade inflammation in the intestinal tract, possibly supported by bacteria-responding CD4+CXCR5+ T cells.

Keywords: B cell; CD4+CXCR5+T cells; Tfh; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / pathology
  • B-Lymphocytes / physiology*
  • Body Mass Index
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Intestines / immunology*
  • Intestines / pathology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • T-Lymphocytes, Helper-Inducer / pathology
  • T-Lymphocytes, Helper-Inducer / physiology*