The loss of Th17 cell populations at mucosal surfaces has been linked to chronic inflammation and microbial translocation.
Key factors in the differentiation of Th17 cells are signal transducer and the activator of transcription 3 (Stat3) and retinoic acid receptor-related orphan receptors gamma (RORγ) and alpha (RORα).
These cytokines are produced by activated antigen presenting cells (APCs) after contact with pathogens.
[10] Thus, three T helper cell subsets are able to influence the myeloid part of the immune system, largely responsible for innate defense against pathogens.
The mechanism of Treg17 cell action is expression of chemokine receptor CCR6, which facilitates trafficking into areas of Th17 inflammation.
[24] Together, excessive activity against autoantigen and prolonged existence of Th17 cells have deleterious consequence in autoimmune disease like Rheumatoid arthritis.
[25] Bone erosion caused by mature osteoclast cells is common in patients with rheumatoid arthritis.
Activated T helper cells such as Th1, Th2, and Th17 are found in the synovial cavity during the time of inflammation due to rheumatoid arthritis.
[29] Microbial translocation results in bacteria moving from out of the gut lumen, into the lamina propria, to the lymph nodes, and beyond into non-lymphatic tissues.
Increasing Th17 cell populations in the intestine has been shown to be both an effective treatment as well as possibly preventative.
Microbial translocation is a major factor that contributes to chronic inflammation and immune activation in the context of HIV.
Because of their immunosuppressive properties, they are thought to decrease the anti-viral response to HIV, contributing to pathogenesis.
Patients continue to exhibit symptoms and do not show as reduced a viral load as expected.
[33] In an SIV-rhesus monkey model, it was found that administering IL-21, a cytokine shown to encourage Th17 differentiation and proliferation, decreases microbial translocation by increasing Th17 cell populations.
[35] A cohort study conducted in Peru demonstrated that individuals who progressed to develop active TB after infection were depleted in Th17 functioning T cells.
[39] Intensive research starting in 2004 in mouse models elucidated its transcription factors and the cytokines that provoke differentiation.