3.3 Th22 Cells
Th22 cells are a recently identified subset of CD4+ T cells. They are named for their notable production of IL-22, along with IL-13, IL-26, TNF-α, and granzyme B52. However, other activated T cells can also secrete IL-22, including Th17 cells, Th1 cells, innate lymphocytes, and some non-lymphocytes53. The production and activation of Th22 cells are dependent on the aromatic hydrocarbon receptor and are positively regulated by IL-6 and TNF-α. IL-22 is expressed predominantly in epithelial cells and keratinocytes and is implicated in skin homeostasis and inflammation54,55. Th22 cells are involved in promoting endothelial cell disorders56 and intestinal epithelial inflammation57 and produce corresponding inflammatory factors. This suggests that Th22 cells exert their inflammatory effects mainly by disrupting the homeostasis of the internal and external surface barriers of various tissues, thus damaging tissues from the outside.
Th22 cells, like other pro-inflammatory cells, have been linked to obesity and IR in recent years, providing a foundation for the onset of T2DM. IL-22 is elevated to varying degrees in the liver, fat, and peripheral blood of individuals with obesity and T2DM58. The levels of IFN-γ, IL-17, and IL-22 are considerably higher in individuals with T2DM than in control individuals, with a positive connection between BMI and homeostasis model assessment (HOMA)-IR59. An overactivated Th22 phenotype adversely correlates with residual islet-cell function, and individuals with T2DM have higher aromatic hydrocarbon receptor gene expression, which promotes a synchronized increase in Th22 and Th1/Th17 cell frequencies60. The majority of naive T cells develop into Th22 cells as a result of IL-6 and TNF-α stimulation55 and are negatively regulated by IL-10. IL-22 induces serum amyloid in a STAT-dependent manner and promotes Th17 activation to disrupt lipid metabolism in the intestinal epithelium61,62. Although several studies have provided evidence for the correlation between Th22 cells and inflammation, as well as IR, the role of IL-22 in the progression of obesity and its related metabolic consequences remains a subject of debate. Further research is required to gain a deeper understanding of this issue.