Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus

Introduction

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and altered lipid metabolism, which is caused mainly by non-functional or lack of secretion of insulin by b pancreatic cells [1]. T2DM is a major health problem worldwide, but it is most notable in low- and middle-income countries, including Mexico [2]. Moreover, obesity-associated chronic inflammation is a key contributing factor to develop T2DM, and several studies have clearly demonstrated that both immune system and metabolism are highly linked [3-5]. Previous studies, such as of Hotamisligil et al. [6], established the concept of obesity-induced inflammation demonstrating high levels of TNF-a in obese mice with insulin resistance, and this phenomenon was ameliorated after TNF-a neutralization. Subsequently, other cytokines were associated with insulin resistance and diabetes [7]. Also, immune cells were associated to obesity and T2DM [3, 4], especially monocytes and macrophages. Thus, monocytes from T2DM patients exhibit a pro-inflammatory profile, secreting high levels of IL-6, IL-8, TNF-a, and IL-1b [8]. These cytokines induce insulin resistance with inhibition of signaling via the insulin receptor [7]. Interestingly, recent findings have shown that cells from the adaptive immune system could also contribute to inflammation associated to T2DM [3, 9].
Regulatory T cells (Treg) play an important role in the maintenance of homeostasis of the immune system [3]. These cells prevent inflammatory responses, through the suppression of effector T cells to self-antigens, commensal microorganisms, allergens, and pathogens [10]. On the other hand, Th17 cells are characterized by producing IL-17. The IL-17 is comprised of a family of cytokines such as IL-17A to IL-17F. The IL-17A is the most important member, because it promotes inflammation through the activation of several cells including monocytes, fibroblasts, and endothelial cells, which produce pro-inflammatory cytokines as well as the stimulation, mobilization, recruitment, and activation of granulocytes [11, 12]. Furthermore, visceral adipose tissue demonstrated that CD4+Th1 cells and CD4+CD25h Treg play an important role in the regulation of body weight, adipocyte hypertrophy, insulin resistance, glucose tolerance, and T2DM progression in both mice and humans [13, 14]. Another study showed that cells producing IL-17 depended on the pro-inflammatory cytokine IL-6 in spleen of obese...


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