Thread by @3DiMMUNE

A new paper in @sciencemagazine from #Belkaid lab at #NIH described an #alternative differentiation #pathway for #commensal-specific T cells in presence of inflammation. Do the data presented support conclusions? Let's dive in.

science.sciencemag.org/content/363/64…

1. #Commnesal S. epidermidis–specific -#MIIINA:H2-M3+ CD8+ T cells ordinarily differentiate into Tc1 or Tc17 subsets. However, when co-exposed to chitin or sand fly (source of #inflammation), Tc17 subset also produce type II cytokines.

2. In such condition, type II #cytokines such as IL-5 or IL-13 are produced by CCR6+ Tc17 cells (out of which 30% are IL-17+). However, there is no overlap between IL-17+ and IL-5+/IL-13+ CD8+ T cells. So, the authors conclusion about "paradoxical phenotype" is unsubstantiated.

3. In any case, such deviation into type II cytokine+ lineage during co-exposure to S. epidermidis and inflammation is specific for CD8+CCR6+ cells (referred to as Tc17).

4. Though, again, there is no actual overlap between IL-17+ T cells and IL-13 or IL-5 producing T cells. so, "the coexpression of classically antagonistic transcription factors" #RORgt and #GATA3 does not change separation of functions between IL-17+ and IL-13+ cells.

5. The authors tried to show how skin #Treg deficiency could have the same effect on Tc17 de-differentiation. Again. the authors failed to show that IL-17+ and IL-5/IL-13+ Tc17 cells overlap. They don't. They put in suppl material these #data. Should be in main paper.

6. Next the authors screened several #cytokines that could mediate this de-differentiation of Tc17 into Tc2 cells. Found several ones, such as IL-18, surprise, surprise.

7. But again, no evidence is provided that IL-17+ T cells co-express IL-5 or IL-13 when exposed to IL-18. Exactly opposite. No overlap.

8. In the end, the authors used "epithelial tongue length" assay as a surrogate for wound healing to show that type II cytokines produced by Tc17 cells are important for wound healing. But we already said that actual Tc17 and Tc2 do not overlap at cytokine level.

So, what is my conclusions: this paper does not support the authors' conclusions about Tc17 acquiring Tc2 phenotype. Yes, it is true that RORgt+ or CCR6+ CD8+ T cells could acquire Tc2 phenotype but the same not true IL-17+ Tc17 cells or at least data are not there.