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-γt⁺ 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 context-dependent understanding of the impact of IL-6 on T cell subsets might inform rational IL-6-directed interventions in autoimmunity and chronic inflammation.