Abstract
The T helper 17 (Th17) cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features. Th17 cells bridge innate and adaptive immunity against fungal and bacterial infections at skin and mucosal barrier surfaces. Although Th17 cells have been extensively studied in the context of autoimmunity, their role in various other pathologies is underexplored and remains an area of open investigation. This review summarizes the history of Th17 cell discovery and the current knowledge relative to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis. We further discuss the concept of Th17 pathogenicity in the context of autoimmunity, cancer, and HIV infection, and we review the most recent discoveries on molecular mechanisms regulating HIV replication/persistence in pathogenic Th17 cells. Finally, we stress the need for novel fundamental research discovery-based Th17-specific therapeutic interventions to treat pathogenic conditions associated with Th17 abnormalities, including HIV infection.
Highlights
The T helper 17 (Th17) cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features
Viruses 2017, 9, 303 later, experiments performed by Cua et al demonstrated that IL-23 but not IL-12 was responsible for the induction of experimental autoimmune encephalitis (EAE), a model of human multiple sclerosis (MS) [12]
Several groups demonstrated that a combination of IL-6, IL-1β, and IL-23 is sufficient for the development of human Th17 cells [124,125,126] and that the requirement of TGF-β is not essential [65,127]
Summary
The Th17 cells represent a major lineage of CD4+ T-cells producing the signature cytokine IL-17A that acts on epithelial cells, contributing to the maintenance of the first line of defense against pathogens at barrier surfaces [1,2,3,4]. IL-23 and IL-12 in response to distinct pathogen-associated molecular patterns (PAMPs) further extended our understanding of the Th1 versus Th17 decision fate making. In 2005, the scientific community acknowledged the existence of a new subset of CD4+ T-cells distinct from Th1 and Th2, a subset that is referred to as Th17 cells [16,17] At this time, many other T-cell lineages have been described including regulatory T cells (Tregs), follicular helper T-cells (Tfh), as well as IL-9 (Th9), and IL-22-producing T-cells (Th22) [18,19,20,21,22]. It is to be anticipated that the constantly evolving technological advances will allow future identification of other novel T-cell lineages with specific functions in immunity and disease pathogenesis
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