Impact of interleukin-32α on T helper cell-related cytokines, transcription factors, and proliferation in patients with type 2 diabetes mellitus

The ability of interleukin (IL)-32α to induce T helper (Th) 1, Th17, and Treg cytokines (interferon gamma [IFN-γ], IL-17, and IL-10, respectively), and transcription factors ([signal transducer and activator of transcription (<i>STAT</i>) 1 and <i>T-box</i> (<i>T-bet</i>) for Th1, <i>STAT3</i> and retinoid-related orphan receptor (<i>ROR</i>)<i>-γt</i> for Th17, and <i>STAT5</i> and forkhead box P3 (<i>Foxp3</i>) for Treg]) were investigated in type 2 diabetes mellitus (T2DM). IL-32α effects on Th cell proliferation and related factors including IL-2 and <i>NF-κB</i> were also explored. Serum levels of IL-32α in 31 patients and 31 healthy controls (HCs) were determined by ELISA assay. CD4⁺ T cells cultured with polyclonal activators in the presence and absence of recombinant IL-32α (rIL-32α). Gene expressions in cultured Th cells were assessed with real-time PCR. Cytokines in supernatants were measured with ELISA. Proliferation experiments were assessed by flow cytometry. The patients showed significant increase in IL-32α levels compared with HCs and its levels were positively correlated with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). rIL-32α enhanced IL-17 and IL-2 production, increased <i>ROR-γt</i> and <i>NF-κB</i> expression, and enhanced Th proliferation in both patients and HCs. In patients, IL-17, <i>ROR-γt</i>, <i>NF-κB,</i> and proliferation levels were higher than those in HCs, in cultures with and without rIL-32α (rIL-32α⁺ and rIL-32α^-). IL-2 levels in rIL-32α⁺cultures of patients were significantly higher than the HCs, and it was positively correlated with proliferation rate and <i>NF-κB</i> expression. Aberrant IL-32α levels are participated in T2DM pathogenesis. IL-32α potently induces Th17-related factors and amplifies the proliferative function of T cells.HighlightsEnhanced serum levels of IL-32α in T2DM patients was correlated with FPG and HbA1c.IL-32α increases <i>ROR-γt</i> expression and IL-17 production, and induces Th17 cells.IL-32α enhances <i>NF-κB</i> expression and IL-2 production, and promotes Th proliferation.IL-32α is more effective for inducing Th17 cells and proliferation in the patients.IL-32α axis could be mentioned as a future therapeutic goal for the T2DM. Enhanced serum levels of IL-32α in T2DM patients was correlated with FPG and HbA1c. IL-32α increases <i>ROR-γt</i> expression and IL-17 production, and induces Th17 cells. IL-32α enhances <i>NF-κB</i> expression and IL-2 production, and promotes Th proliferation. IL-32α is more effective for inducing Th17 cells and proliferation in the patients. IL-32α axis could be mentioned as a future therapeutic goal for the T2DM.