RETRACTED: Monocytes play different roles in stimulating T cells in obese diabetic individuals

Abstract

Type 2 diabetes (T2D) is a chronic metabolic disorder, which was also found to involve a series of inflammatory disorders, including accumulation of macrophages and T cells in the adipose tissue, increased proinflammatory cytokine production, shifting of macrophage composition toward M1-type, and skewing of peripheral blood T cells toward IL-17 productions. However, these studies were primarily conducted in obese mouse models and/or human subjects with higher BMI, and may not reflect the role of the immune system in non-obese T2D pathogenesis. Here, we examined T cell and monocyte cytokine expression and function in both non-obese and obese T2D patients. We found that IFN-g production by circulating T cells were increased in both non-obese and obese T2D subjects, while IL-17 is only upregulated in obese T2D subjects. Also, circulating monocytes from obese T2D subjects had significantly higher IL-6 production than their counterparts in non-obese T2D subjects. Moreover, monocytes from non-obese T2D subjects could support IFN-g but not IL-17 production in vitro, while that from obese T2D subjects supported both IFN-g and IL-17 production. Together, our results revealed that the role immune system plays in T2D pathogenesis is more complicated than previously thought, and is affected by the person's BMI.

Correlation Among Hypoglycemia, Glycemic Variability, and C-Peptide Preservation After Alefacept Therapy in Patients with Type 1 Diabetes Mellitus: Analysis of Data from the Immune Tolerance Network T1DAL Trial

“…Components of both innate and adaptive immunity contribute to insulin resistance in diabetes and hence biologic agents may have complex effects on glycemic control and variability. 33 For example, both TNFα and IL-6 influence insulin signaling, 34, 35 but the potential consequences of this in the context of TNFα or IL-6 blockade in T1D are unknown. Lastly, while it is clear that poor glycemic control is related to the development of microvascular complications including retinopathy, this process also involves pro-inflammatory cytokines such as TNFα and IL-1β.…”

Monocyte-mediated inflammation and cardiovascular risk factors in type 2 diabetes mellitus: A systematic review and meta-analysis of pre-clinical and clinical studies

“…In total, the included studies comprised of 2168 participants of which 1065 (49.8%) were living with T2DM and 1103 (50.6%) were normal individuals. Of the included 20 human studies, 18 were cross-sectional [5][6][7][8][9][11][12][13][14][15][16][17][18][19][20]24,25 and 2 were cohort studies. 4,26 The mean age of the study population was 52.28 AE 8.07 with a male to female ratio of 1.39 (Table 1S).…”

“…The publication trends on monocyte function in T2DM in both human and animal studies are presented in Figure 1S. Briefly, 2 studies were published between 2001 and 2005, 9,12 5 studies between 2006 and 2010, 7,11,13,20,27 10 studies between 2011 and 2015 1,4,6,10,[14][15][16]18,19,24 and another 10 studies from 2016 to 2019. 3,5,8,14,17,25,26,[28][29][30] The included studies were spread across Europe, Asia and United States with most of the studies from the United States ( Figure 1S).…”

“…4,15,[17][18][19][20] Several studies have reported on increased monocyte activation in patients living with T2DM when compared to healthy controls. 4,15,18,19 In contrast, others have reported no significant differences in monocytes levels between T2DM and control groups. 6,11 The exact role of monocytes in the pathogenesis of T2DM remains elusive.…”

BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer

“…Th17 cells are a pro-inflammatory subset of T helper cells (characterized by secretion of IL-17A, IL-17F, and IL-6) that frequently associate with autoimmunity and inflammatory diseases [58, 59]. Only monocytes from obese individuals with T2D (as opposed to lean individuals with T2D) support IL-17 production from T cells in vitro [60]. The disproportionate importance of Th17 mechanisms in human T2D was most convincingly shown by recent work that identified a pro-inflammatory Th17 cytokine signature, which differentiates subjects with T2D from metabolically healthy subjects, irrespective of BMI [18], and predicts T2D status with higher than random fidelity.…”