The immune system contains highly specialized cells, one of which is the T helper 17 cell, or Th17 cell. These cells are a type of T helper cell, which means they coordinate and activate other parts of the immune response rather than neutralizing threats directly. The Th17 response is a targeted defense mechanism named for the cell’s production of a signaling protein, Interleukin-17 (IL-17). Understanding this branch of the immune system offers insight into how the body protects itself and how this protection can go awry, leading to disease.
The Role of Th17 Cells in Immunity
The primary function of Th17 cells is to guard the body’s mucosal surfaces, such as the linings of the gut, respiratory tract, and skin. Positioned in these barrier tissues, they act as sentinels that can quickly rally a defense against invading microbes by mounting a localized inflammatory response.
Th17 cells are adept at combating extracellular pathogens, which are invaders that live outside of host cells. This includes certain types of bacteria and fungi. For example, they are instrumental in clearing fungal infections like Candida albicans and defending against bacteria such as Klebsiella pneumoniae.
To accomplish this, Th17 cells release their signature protein, IL-17, along with other signaling molecules like IL-22. These signals act on the nearby epithelial cells that form the mucosal barrier. This communication prompts the epithelial cells to produce antimicrobial substances and to release signals that recruit other immune cells, most notably neutrophils, to the site of infection.
Activation of the Th17 Response
The Th17 response is initiated when the body detects a specific threat, beginning with unspecialized immune cells known as naive CD4+ T cells. The decision for these cells to become Th17 cells depends on chemical signals received from other immune cells that have encountered a pathogen.
This transformation is driven by cytokines. When innate immune cells like dendritic cells detect certain bacteria or fungi, they release a mix of cytokines. The combination of transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6) provides the primary signal for a naive T cell to become a Th17 cell by activating a master genetic switch, the transcription factor RORγt.
Once differentiation is underway, another cytokine, Interleukin-23 (IL-23), is necessary to stabilize and expand the population of newly formed Th17 cells. IL-23 ensures these cells survive and remain committed to their function. This multi-signal process ensures the Th17 response is tightly controlled.
The Link to Autoimmune and Inflammatory Diseases
While the Th17 response is protective, its inflammatory power can cause significant damage if it becomes dysregulated. In autoimmune diseases, the immune system mistakenly attacks the body’s own tissues. An overactive or misdirected Th17 response is a feature in many of these conditions, driving chronic inflammation and tissue destruction.
Psoriasis is a clear example of Th17-driven pathology. In this condition, an abundance of Th17 cells in the skin release IL-17, which causes skin cells to over-proliferate and form plaques. This same pathway contributes to psoriatic arthritis when the inflammation extends to the joints.
In rheumatoid arthritis, Th17 cells infiltrate the tissue lining the joints, releasing cytokines that stimulate enzymes to break down cartilage and bone. In multiple sclerosis, Th17 cells cross the blood-brain barrier to attack the myelin sheath that insulates nerve fibers, disrupting nerve signals and causing neurological symptoms.
The gut is another common site of Th17-mediated damage. In inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, a dysregulated Th17 response to gut microbes contributes to chronic intestinal inflammation and the tissue damage characteristic of the disease.
Therapeutic Targeting of Th17 Pathways
The understanding of the Th17 pathway’s role in autoimmune diseases has led to highly specific treatments. Instead of medications that suppress the entire immune system, biologic drugs can block specific components of the Th17 response. These treatments are often monoclonal antibodies, lab-produced molecules that attach to specific proteins.
One class of these drugs directly targets IL-17A, the primary cytokine produced by Th17 cells. By neutralizing IL-17A, drugs such as secukinumab and ixekizumab prevent it from signaling to other cells, interrupting the inflammatory cascade in diseases like psoriasis and psoriatic arthritis.
Another strategy involves blocking IL-23, the cytokine responsible for stabilizing and activating Th17 cells. Drugs like ustekinumab, guselkumab, and tildrakizumab prevent the maintenance and expansion of the pathogenic Th17 cell population. This approach has proven effective in treating psoriasis, psoriatic arthritis, and Crohn’s disease.