TGF-β1 Drives Inflammatory Th Cell But Not Treg Cell Compartment Upon Allergen Exposure

TGF-beta 1 is known to have a pro-inflammatory impact by inducing Th9 and Th17 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-beta is a major player in AAI by driving effector T cells, while Tregs differentiate independently. Induction of experimental AAI and airway hyperreactivity in a mouse model with inducible genetic ablation of the gene encoding for TGF beta-receptor 2 (Tgfbr2) on CD4(+)T cells significantly reduced the disease phenotype. Further, it blocked the induction of pro-inflammatory T cell frequencies (Th2, Th9, Th17), but increased Treg cells. To translate these findings into a human clinically relevant context, Th2, Th9 and Treg cells were quantified both locally in induced sputum and systemically in blood of allergic rhinitis and asthma patients with or without allergen-specific immunotherapy (AIT). Natural allergen exposure induced local and systemic Th2, Th9, and reduced Tregs cells, while therapeutic allergen exposure by AIT suppressed Th2 and Th9 cell frequencies along with TGF-beta and IL-9 secretion. Altogether, these findings support that neutralization of TGF-beta represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs cells.

Automated summary

TGF-beta plays a critical role in allergic airway inflammation by driving effector T cells and influencing the disease outcome. Inhibiting TGF-beta can reduce the disease phenotype, decrease pro-inflammatory T cell frequencies, and increase anti-inflammatory T cell frequencies. Additionally, in patients with allergic rhinitis and asthma, allergen-specific immunotherapy can suppress Th2 and Th9 cell frequencies and decrease the secretion of TGF-beta and IL-9.