TH17 cells, known for secreting IL-17, play a role in host defence and inflammation. While conventional TH17 cells arise in the periphery, recent work identified a population of natural TH17 (nTH17) cells developing directly in the thymus. These cells differ from conventional CD4+ thymocytes and peripheral TH17 cells in several key ways.
- TCR specificity: nTH17 cells show skewed usage of the Vβ3 TCR chain.
- Developmental requirements: Their differentiation requires MHC class II expression on medullary thymic epithelial cells, but not cortical ones.
- Signaling pathways: Defective TCR signaling (e.g., SLP76 mutations) leads to increased nTH17 cells in the thymus but impairs peripheral TH17 differentiation in the intestine.
These findings suggest that thymic-derived nTH17 cells and peripherally induced TH17 cells are distinct populations with separate developmental controls. This work highlights the thymus as a direct source of IL-17–producing T cells, adding complexity to how TH17-mediated immunity and pathology are regulated.
Journal article: Kim, J. S. et al. 2025. The requirements for natural Th17 cell development are distinct from those of conventional Th17 cells. J. Exp. Med.
Summary by Stefan Botha
