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T helper 17 cells (Th17) Th17 helper cells are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that encourage Th17 differentiation discourage Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces, but they have also been implicated in autoimmune and inflammatory disorders. The loss of Th17 cell populations at mucosal surfaces has been linked to chronic inflammation and microbial translocation.

Th17 cells in disease

The dysregulation of Th17 has been associated with autoimmune disorders and inflammation. In the case of autoimmune disorders, Th17 cell over activation can cause an inappropriate amount of inflammation, like in the case of rheumatoid arthritis. Th17s have also been shown to be necessary for maintenance of mucosal immunity. In HIV, the loss of Th17 cell populations can contribute to chronic infection.

Loss of Th17 cells in HIV infection

The depletion of Th17 cell populations in the intestine disrupts the intestinal barrier, increases levels of movement of bacteria out of the gut through microbial translocation, and contributes to chronic HIV infection and progression to AIDS. Modulating Th17 cell populations has been shown to be both an effective treatment as well as possibly preventative.

Although all CD4+ T cells gut are severely depleted by HIV, the loss of intestinal Th17 cells in particular has been linked to symptoms of chronic, pathogenic HIV and SIV infection. Microbial translocation is a major factor that contributes to chronic inflammation and immune activation in the context of HIV. (fung) Th17 cells prevent severe HIV infection by maintaining the intestinal epithelial barrier during HIV infection in the gut (pallikuth). Because of their high levels of CCR5 expression, the coreceptor for HIV, they are preferentially infected and depleted (bixler).

Additionally, the loss Th17 cells in the intestine leads to a loss of balance between inflammatory Th17 cells and Treg cells, their anti-inflammatory counterparts. Because of their immunosuppressive properties, they are thought to decrease the anti-viral response to HIV, contributing to pathogenesis (Favre 2009).

Revitalizing Th17 cells has been shown to decrease symptoms of chronic infection, including decreased inflammation, and results in improved responses to highly active anti-retroviral treatment (HAART) (brenchley). In an SIV-rhesus monkey model, Pallikuth et al. (2013) found that administering IL-21, a cytokine shown to encourage Th17 differentiation and proliferation, decreases microbial translocation by increasing Th17 cell populations. It is hopeful that more immunotherapies targeting Th17 cells could help patients who do not respond well to HAART.