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.