TH22 cells are a distinct population of T helper cells. These specialized immune cells contribute to the body’s defense mechanisms. As a more recently identified group, their unique functions are still being actively explored, adding to our understanding of the complex human immune system.
Distinct Characteristics of TH22 Cells
TH22 cells are distinguished by their production of Interleukin-22 (IL-22), a cytokine that sets them apart from other T helper cell subsets like Th1, Th2, and Th17 cells. IL-22 predominantly targets non-immune cells, particularly those in barrier tissues. This unique targeting mechanism highlights their role in maintaining tissue integrity and defense.
These cells are commonly found in barrier tissues, including the skin, gut, and lungs, where they contribute to local immune responses. Their development from naive T cells is influenced by specific cellular signals and transcription factors, such as the aryl hydrocarbon receptor (AHR) and retinoid-related orphan receptor gamma t (RORĪ³t). TH22 cells also express distinct chemokine receptors, including CCR4, CCR6, and CCR10, which facilitate their migration to these specific tissue sites.
The IL-22 produced by TH22 cells binds to a specific receptor complex on target cells, composed of IL-22R1 and IL-10R2 subunits. This receptor is widely expressed on epithelial and stromal cells but is generally absent on hematopoietic (immune) cells. This selective expression pattern explains why IL-22 primarily influences non-immune tissue cells, promoting their proliferation, survival, and the production of antimicrobial substances.
TH22 Cells in Maintaining Health
TH22 cells contribute to the body’s well-being by supporting the protective functions of barrier tissues. The IL-22 they produce helps maintain the integrity of the skin, gut lining, and respiratory tract. For example, in the skin, IL-22 promotes the proliferation and differentiation of keratinocytes, strengthening the physical barrier against pathogens and environmental insults.
These cells are also involved in tissue repair and wound healing. IL-22 stimulates the growth and migration of epithelial cells, which is important for closing wounds and restoring damaged tissue structures. This action helps in the rapid recovery of injured areas.
TH22 cells also play a role in direct antimicrobial defense. The IL-22 they secrete induces epithelial cells to produce various antimicrobial peptides, such as S100 proteins and defensins. These peptides act as natural antibiotics, directly combating certain bacteria and fungi at barrier surfaces, contributing to the body’s innate immunity.
TH22 Cells in Disease
When their activity is not properly regulated, TH22 cells can contribute to various disease states. In inflammatory and autoimmune conditions, their involvement can exacerbate inflammation or tissue damage. For instance, in psoriasis, a chronic inflammatory skin disease, elevated levels of TH22 cells and IL-22 are often observed in affected skin. IL-22 contributes to the abnormal proliferation of keratinocytes, a hallmark of psoriasis, and can induce the expression of inflammatory mediators.
In inflammatory bowel disease (IBD), TH22 cells and IL-22 have a complex role, sometimes promoting inflammation and sometimes offering protection, depending on the specific context and stage of the disease. In rheumatoid arthritis (RA), a chronic autoimmune disease affecting joints, increased levels of TH22 cells and IL-22 are found in the synovial tissue, where IL-22 can induce the proliferation of synovial fibroblasts and contribute to the inflammatory response and bone erosion.
The role of TH22 cells in cancer is also intricate and can be contradictory. In some cancers, such as certain types of colorectal cancer and hepatocellular carcinoma, elevated levels of IL-22 or TH22 cells can promote tumor growth by stimulating the proliferation of malignant epithelial cells. However, in other contexts, the physiological functions of TH22 cells, like tissue repair, might exert an anti-tumor effect, highlighting the nuanced involvement of these cells in cancer progression.