Interleukin-17-producing T-cells (Th17) is one of the major CD4+ T-lymphocyte subtypes that mediate immunity in mammals. In comparison to the other T-cell subsets, Th17 are present in very low amounts in human blood but are highly elevated during chronic inflammation and are implicated in many autoimmune diseases. Currently, reasons for the remarkable success of Th17 cells as etiologic agents is unknown and in this study, we have investigated mechanisms that may explain the frequent involvement of Th17 cells in the etiology of organ-specific autoimmune diseases, such as uveitis and multiple sclerosis. Data derived from our studies have provided mechanistic explanation for the high pathogenicity of Th17 cells in autoimmune diseases. Our genetic ablation experiments in mice revealed that the quintessential Th17 transcription-factor, STAT3, collaborates with Class-O Forkhead transcription-factors in conferring survival advantages to Th17 phenotype. Our results also suggest that STAT3 is convergence point for mechanisms that regulate lymphocyte quiescence and those controlling T-cell activation and survival. Thus, similar to their role in regulating lifespan of Caenorhabditis elegans, we show that through its collaboration with STAT3 that FoxO functions extend to regulating lifespan of lymphoid cells.
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