Type 2 Innate Lymphoid Cells: Protectors in Type 2 Diabetes

Abstract

Type 2 innate lymphoid cells (ILC2) are the innate counterparts of Th2 cells and are critically involved in the maintenance of homeostasis in a variety of tissues. Instead of expressing specific antigen receptors, ILC2s respond to external stimuli such as alarmins released from damage. These cells help control the delicate balance of inflammation in adipose tissue, which is a determinant of metabolic outcome. ILC2s play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) through their protective effects on tissue homeostasis. A variety of crosstalk takes place between resident adipose cells and ILC2s, with each interaction playing a key role in controlling this balance. ILC2 effector function is associated with increased browning of adipose tissue and an anti-inflammatory immune profile. Trafficking and maintenance of ILC2 populations are critical for tissue homeostasis. The metabolic environment and energy source significantly affect the number and function of ILC2s in addition to affecting their interactions with resident cell types. How ILC2s react to changes in the metabolic environment is a clear determinant of the severity of disease. Treating sources of metabolic instability via critical immune cells provides a clear avenue for modulation of systemic homeostasis and new treatments of T2DM.

Imbalanced distribution of group 2 innate lymphoid cells (ILCs) and ILC precursors in peripheral blood of patients with primary biliary cholangitis

“…29,30 In addition, ILC2s have been reported to play a protective role in colitis by modulating IL-33/ST2 pathway and Treg levels 31 ; these cells contribute to maintaining the balance in inflammation in the adipose tissue to exert an anti-inflammatory function in type 2 diabetes mellitus. 32 CCR6 was expressed on the surface of ILC2s 9,33 ; further, the CCR6 ligand CCL20 could be secreted by senescent biliary epithelial cells in PBC. 34 Therefore, the proportions of circulating ILC2s were decreasing in patients with PBC, which also may be associated with the recruitment of ILC2s into injured biliary epithelial cells in PBC for CCL20 release.…”

“…ILC2s were mainly involved in the promotion of allergic airway inflammation, chronic rhinosinusitis and atopic dermatitis during abnormal activation 29 ; however, ILC2s also played a protective function by promoting expansion and differentiation of Th2 cells, interacting with Tregs and transforming the immune response towards a type 2 phenotype to suppress inflammation 29,30 . In addition, ILC2s have been reported to play a protective role in colitis by modulating IL‐33/ST2 pathway and Treg levels 31 ; these cells contribute to maintaining the balance in inflammation in the adipose tissue to exert an anti‐inflammatory function in type 2 diabetes mellitus 32 . CCR6 was expressed on the surface of ILC2s 9,33 ; further, the CCR6 ligand CCL20 could be secreted by senescent biliary epithelial cells in PBC 34 .…”

Gut microbiota dysbiosis as an inflammaging condition that regulates obesity-related retinopathy and nephropathy

“…On the one hand, the circulating levels of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), and IL-6 were significantly increased and resulted in T2DM in obese humans and high-fat diet (HFD)-induced obese mice ( Luck et al, 2015 ; Zhou et al, 2018 ; Scheithauer et al, 2020 ). On the other hand, obesity-induced fatty accumulation in tissues such as liver, muscle, pancreas, brain, and adipose tissue imbalances the immune system, including elevated proinflammatory immune cells (M1 macrophages, CD8 + T cells, Th1 T cells, B cells, and natural killer (NK) cells) and reduced anti-inflammatory immune cells [M2 macrophages, regulatory T cells (Tregs), and type 2 innate lymphoid cells (ILC2s)], which ultimately results in the development of T2DM ( Schwartz et al, 2016 ; Winer et al, 2016 ; Reilly and Saltiel, 2017 ; Painter and Akbari, 2021 ).…”

Heterogeneity of Group 2 Innate Lymphoid Cells Defines Their Pleiotropic Roles in Cancer, Obesity, and Cardiovascular Diseases

“…It is often associated with type 2 diabetes, high blood pressure, hyperlipidemia, and cardiovascular diseases ( 95 ). Apart from the roles of ILC2s in typical Th2 immune responses, they also contribute to homeostatic and metabolic regulation in adipose tissues ( 96 , 97 ). Adipose tissues are categorized into white, brown, and beige.…”