The laboratory of Joonsoo Kang provides us with a very nice example of how to follow up a resource paper published in Nature Immunology Narayan et al 2012 that had performed a genome wide gene expression analysis specifically associated with Vγ chain restriction. This month they describe the minimal core transcriptional requirement, which is formed with SOX4, SOX13, TCF1 and LEF1, and that controls the generation of IL-17-producing γδ T cells.
In this work they ask as to whether all innate like cell types that produce IL-17 and/or IL-22 express an unifying genetic profile that could suggest they share a similar program of differentiation. Besides αβ T helper cells and γδ T cells there are also invariant NKT, LTi-like, NKp46+ NCR22, and ILC17 cells (with the latter three subsets primarily localized in the GALT) that produce IL-17 and/or IL-22.
This paper is important for it starts to provide insights into the mechanisms that control thymic precommitment of IFN-γ- and IL-17-producing γδ T cells.
In conclusion, more work is required to fully understand the emergence of IL-17-producing γδ T cells but I recommend to have a look at these data “A Network of High-Mobility Group Box Transcription Factors Programs Innate Interleukin-17 Production.”.
Of note, I would like to stress that they have a completely different approach than us. They use Vγ chain usage to segregate effector functions, while we resort on surface markers instead, such as CD27 and CCR6. I feel this gives some contradiction to this work since the expression of these transcription factors precedes that of the TCR and that they clearly show no specific requirement for TCR signalling to generate IL-17-producing γδ T cells. They use an elegant strategy to ask the following question: if the TCR is deterministic for effector fate, expression of a functional Vγ4 TCR in all γδ T cells should enhance the generation of Tγδ17 cells. The Tg mice, however, did not produce a significantly enhanced number of IL-17+ γδ cells.