Activity of Group 2 Innate Lymphoid Cells is Associated with Chronic Inflammation and Dysregulated Metabolic Homoeostasis in Type 2 Diabetic Nephropathy

Abstract

The metabolic syndrome (MS) is an independent risk factor for type 2 diabetic nephropathy and accompanied by subclinical inflammation which involves immune-deriving factors. Emerging studies indicate that group 2 innate lymphoid cells (ILC2s) can regulate adipose metabolism, but much less is known about the activity of ILC2s in metabolic imbalance in obesity and diabetes. This study explored the effect of ILC2s-related molecules on the occurrence of MS in type 2 diabetic nephropathy. Thirty patients with type 2 diabetic nephropathy were included in the study; the mRNA expression of ILC2s-associated molecules from peripheral blood mononuclear cell and the correlation of the ILC2s activity and the MS-related indicators were analysed. The results indicated that the waist circumference, fasting blood glucose, systolic blood pressure, diastolic blood pressure and triglyceride in patients with simple diabetes and diabetic nephropathy were increased, and the incidence of MS was 46.67% and 86.67%, respectively. The ILC2s-associated factors RORα, T1/ST2 and IL-5/IL-13 mRNA were increased in diabetic nephropathy. There was a positive correlation between the expression level of IL-13 or T1/ST2 mRNA and some MS indexes. In addition, the levels of plasma sTNFR, eotaxin-2 and I-309 were also increased in patients with type 2 diabetic nephropathy. It suggested that the patients with type 2 diabetic nephropathy were more likely to have multiple components of MS than those with simple type 2 diabetes mellitus, and enhanced ILC2s activity might be involved in the formation of MS in diabetic nephropathy via influencing blood pressure and lipid metabolism.

An update on immune dysregulation in obesity‐related insulin resistance

“…In the absence of ILC2, the numbers of AT‐resident eosinophils and M2‐like macrophages are significantly reduced . Recently, Lu et al have shown that increased activity of ILC2s in T2D patients with nephropathy causes chronic inflammation and abnormal metabolic homeostasis . Oldenhove et al revealed that in HFD‐fed mice, elevated levels of TNF‐ɑ and IL‐33 in the AT increase the expression of programmed cell death‐1 (PD‐1) on ILC2s and impair their functions in the presence of PD‐L1 + M1‐like macrophages .…”

“…6 Recently, Lu et al have shown that increased activity of ILC2s in T2D patients with nephropathy causes chronic inflammation and abnormal metabolic homeostasis. 132 Oldenhove et al revealed that in HFD-fed mice, elevated levels of TNF-ɑ and IL-33 in the AT increase the expression of programmed cell death-1 (PD-1) on ILC2s and impair their functions in the presence of PD-L1 + M1-like macrophages. 133 O'Sullivan et al have shown that after HFD in mice, immune cell-derived IL-12 in the AT causes rapid proliferation and activation of IFN-γ-producing ILC1s, which induce macrophage polarization towards M1-like phenotype and promote IR.…”

Th2 cells as an intermediate for the differentiation of na�ve T cells into Th9 cells, associated with the Smad3/Smad4 and IRF4 pathway

“…Pre-denaturation was performed at 95˚C for 5 min, denaturation was performed at 95˚C for 30 sec, annealing was performed at 72˚C for 30 sec and extension was performed at 65˚C for 1 min. Fold changes in the expression of each gene relative to β-actin were calculated using the comparative threshold cycle (Ct) method (13). All experiments were performed in triplicate.…”

Innate Lymphoid Cells in Renal Inflammation

“…Since two independent studies suggested increased numbers of ILC2s and type 2 cytokines (IL-4, IL-5, IL-13) in the peripheral blood of patients suffering from CKD due to type 2 diabetes (45,46), it can be speculated that ILC2s might be a marker for renal fibrosis in human CKD. However, technical limitations in the flow cytometry gating strategy used to identify ILC2s in these studies preclude valid conclusions from these data and further research is clearly needed to assess a potential role of ILC subsets in human CKD.…”