TGF-β1 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-β 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 TGFβ-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-β and IL-9 secretion. Altogether, these findings support that neutralization of TGF-β represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs cells.

众所周知，TGF-β1 通过诱导 Th9 和 Th17 细胞具有促炎作用，同时它还诱导抗炎 Treg 细胞 (Tregs)。在过敏性气道炎症 (AAI) 的背景下，它的双重作用对于影响疾病的结果至关重要。在这里，我们通过驱动效应 T 细胞证明 TGF-β 是 AAI 的主要参与者，而 Tregs 独立分化。在小鼠模型中诱导实验性 AAI 和气道高反应性，可诱导基因消融编码 TGFβ 受体 2 的基因（TGFBR2) 在 CD4 ⁺T细胞显着降低了疾病表型。此外，它阻断了促炎 T 细胞频率（Th2、Th9、Th17）的诱导，但增加了 Treg 细胞。为了将这些发现转化为人类临床相关背景，在接受或不接受过敏原特异性免疫治疗 (AIT) 的过敏性鼻炎和哮喘患者的诱导痰和全身血液中对 Th2、Th9 和 Treg 细胞进行了定量。自然过敏原暴露诱导局部和全身 Th2、Th9 和 Tregs 细胞减少，而 AIT 的治疗性过敏原暴露抑制 Th2 和 Th9 细胞频率以及 TGF-β 和 IL-9 分泌。总而言之，这些发现支持 TGF-β 的中和代表了过敏和哮喘的可行治疗选择，不会通过影响 Tregs 细胞而造成免疫失调的风险。