Fatty Acid Binding Protein 4 Regulates the Antigen-Presenting Function of Dendritic Cells Resulting in T Cell Priming in Streptozotocin-Induced Type 1 Diabetes Mice.

BACKGROUND

Type 1 diabetes is an autoimmune disease with progressive destruction of insulin-producing β cells in islets of Langerhans of the pancreas. However, the early pathogenic factors triggering the recruitment and activation of innate immune cells remain unclear. A study reported that FABP4 accelerates the onset of type 1 diabetes in NOD mice by inducing the polarization of proinflammatory macrophages and their infiltration into pancreatic islets. Nonetheless, the role of FABP4 in mediating crosstalk between innate immunity and adaptive immunity in T1D is unclear.

METHODS

Intraperitoneal injections of streptozotocin were used to establish a type 1 diabetes mouse model. Blood glucose was monitored, and intraperitoneal glucose tolerance test (IPGTT) was conducted to compare glucose homeostasis. The peripheral immune cells were detected using flow cytometry. Mixed lymphocyte reactions were applied to examine the function of FABP4 on antigen-presenting in dendritic cells.

RESULTS

We found that genetic ablation of FABP4 in mice alleviated STZ-induced diabetic damage by reducing diabetogenic T lymphocytes and their production of inflammatory cytokines. In vitro studies, FABP4 deficiency dendritic cells expressed lower properties of CD86 and CD80, showing impaired antigen-presenting functions.

CONCLUSIONS

Genetic ablation of FABP4 in mice alleviated STZ-induced diabetic damage by impairing the antigen-presenting function of dendritic cells through downregulating the phosphorylation levels of the ERK and JNK pathways.