Purpose of review: The present review emphasizes the requirement for functional genomic studies and studies in human immunology toward the identification of tissue-specific regulators of human Th17 lineage commitment and molecular determinants for HIV permissiveness in Th17 cells.
Recent findings: Th17 cells play a beneficial role in immunity against bacteria and fungi and a deleterious role in autoimmune diseases. Commensal microbiota control Th17 differentiation in the gut. Th17 cells are depleted from the gut of HIV-infected individuals and their depletion is associated with microbial translocation, which is a cause for chronic immune activation and disease progression. Th17 cells are permissive to HIV infection and therefore play a dual role in HIV pathogenesis.
Summary: The discovery of human Th17 lineage revised our thinking about CD4 T-cell heterogeneity and plasticity in the context of HIV pathogenesis. The present review highlights unsolved mysteries around the genetic control of differentiation and tissue-specific specialization of human Th17 cells. Systems biology studies are now required to provide a global view of transcriptional changes in Th17 subsets and mucosal tissues and to shed light on molecular mechanisms of Th17 depletion in HIV infection, with the final goal to identify new strategies to improve mucosal immunity in infected individuals.