Role of IL-6 in the commitment of T cell subsets

IL-6 gained much attention with the discovery that this cytokine is a non-redundant differentiation factor for Th17 cells and T follicular helper cells. Adaptive immune responses to fungi and extracellular bacteria are impaired in the absence of IL-6. IL-6 is also required for the induction of ROR-gamma t+ Treg cells, which are gatekeepers of homeostasis in the gut lamina propria in the presence of commensal bacteria. Conversely, severe immunopathology in T cell-mediated autoimmunity is mediated by Th17 cells that rely on IL-6 for their generation and maintenance. Recently, it has been discovered that the differentiation of these distinct T helper cell subsets may be linked to distinct signaling modalities of IL-6. Here, we summarize the current knowledge on the mode of action of IL-6 in the differentiation and maintenance of T cell subsets and propose that a contextdependent understanding of the impact of IL-6 on T cell subsets might inform rational IL-6-directed interventions in autoimmunity and chronic inflammation.

Automated summary

IL-6 plays a critical role in the differentiation and maintenance of Th17 cells and T follicular helper cells, as well as in the induction of Treg cells. Its absence can impair adaptive immune responses to fungi and extracellular bacteria, while its presence is necessary for homeostasis in the gut lamina propria.