Differences in group 2 innate lymphoid cells in type 2 or slowly progressive insulin-dependent type 1 diabetes mellitus

Human group 2 innate lymphoid cells (ILC2s) are key regulators of chronic inflammation in type 2 diabetes mellitus (T2DM). In contrast, autoimmune-mediated inflammation is characteristic of type 1 diabetes mellitus (T1DM), particularly slowly progressive insulin-dependent diabetes mellitus (SPIDDM). However, whether ILC2-mediated inflammation observed in T2DM is also present in SPIDDM remains unclear. We hypothesized that ILC2 profiling could help distinguish T2DM from SPIDDM and aimed to characterize ILC2s in Japanese patients. Peripheral blood mononuclear cells (PBMCs) were obtained from Japanese patients with T1DM or T2DM participating in a diabetic cohort study. Ex vivo flow cytometric immunophenotyping was performed, and innate lymphoid cell fractions were quantified using fluorescence-activated cell sorting (FACS). The frequency of ILC2s was determined by FACS, and ILC2 proliferation was assessed ex vivo in PBMCs exposed to saturated fatty acids mimicking conditions of worsening T2DM. Mean (SD) ILC2 frequencies were 5.50 (2.30) % in T2DM and 3.42 (2.16) % in SPIDDM. Frequencies were significantly higher in T2DM than in SPIDDM (p = 0.007) and were also elevated compared with other T1DM subtypes. ILC2 proliferation was influenced by saturated fatty acids associated with T2DM progression. This study demonstrated that numerical differences in ILC2s were observed in T2DM but not in SPIDDM.