Negative correlation between circulating integrin 4⁺ group 3 innate lymphoid cells and the severity of type 2 diabetes

Background: Impaired intestinal barrier and immune dysfunction promote the development of type 2 diabetes (T2D). Group 3 innate lymphoid cells (ILC3s), which are enriched in the intestinal lamina propria, are key for intestinal barrier integrity. However, there is a paucity of data on circulating ILC3s in patients with T2D. Purpose: To examine the characteristics of ILC3s in patients with T2D and identify the relationship between ILC3s and clinical indicators of T2D. Methods: Fifty-nine patients with T2D and thirty controls were enrolled in this retrospective study. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry and plasma cytokine levels were measured by enzyme-linked immunosorbent assays. Results: The proportion of circulating ILC3s in the T2D group was significantly lower than that in controls and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, the proportion of circulating integrin alpha 4(+) ILC3s was also significantly lower in the T2D group and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with GM-CSF. Moreover, the level of circulating integrin alpha 4(+) ILC3s showed a positive correlation with the proportion of circulating dendritic cells (DCs), which was also decreased in patients with T2D and positively associated with GM-CSF. Conclusion: ILC3s, especially integrin alpha 4(+) ILC3s, were decreased in patients with T2D and showed a negative correlation with disease severity. These cell subsets may delay the progression of T2D by promoting DC differentiation via the secretion of GM-CSF.