Researchers have identified a previously unrecognized mechanism driving immune dysfunction in allergic asthma and demonstrated a potential strategy to reverse it — by restoring the function of regulatory T cells (Tregs) through targeted epigenetic reprogramming.
In the paper, “Dectin-1 Epigenetic Reprogramming Rescues Senescent-Like Treg Function in Allergic Asthma,” research showed that regulatory Tregs from patients with allergic asthma acquire a senescent‑like, dysfunctional state marked by shortened telomeres, increased senescence‑associated β‑galactosidase activity, elevated apoptosis and impaired suppressive capacity. These altered Tregs also exhibit a pro‑inflammatory shift in cytokine production, undermining their normal role in controlling airway inflammation, the study’s authors noted. The paper was published in Life Science Alliance.
Investigators found that treating patient‑derived Tregs with KQS‑1, a novel fungal polysaccharide, restored core Treg suppressive function. The treatment re‑established FOXP3‑ and IL‑10-dependent regulatory activity — two signature pathways essential for immune tolerance — while reducing pro‑inflammatory cytokine production.
Further, the recovery depended on Dectin‑1, a C‑type lectin receptor more commonly associated with antifungal immunity, researchers noted. KQS‑1-to-Dectin‑1 binding activated a Raf‑1/ROS signaling pathway, triggering sustained epigenetic changes at the FOXP3 and IL10 gene loci, they noted. These changes included increased activating histone marks, focal DNA hypomethylation and chromatin remodeling that reinforced long‑term gene expression.
When researchers deleted Dectin‑1 using CRISPR gene editing, all beneficial effects of KQS‑1 were lost, confirming that the pathway is essential for Treg rescue, they said.
The authors of the study noted the functional relevance of these findings was supported by in vivo experiments. In a mouse model of allergic asthma, KQS‑1 treatment reduced airway hyperresponsiveness, inflammation and tissue remodeling. In addition, mice receiving adoptive transfer of KQS‑1–trained human Tregs showed marked protection from allergic airway disease, providing proof‑of‑principle evidence that restored Treg function can translate into meaningful physiological benefit, the authors noted.
Rather than attempting to globally rejuvenate immune cells, the researchers proposed a precision epigenetic strategy: selectively reprogramming key regulatory genes to restore immune balance. By focusing on FOXP3 and IL10 — the central drivers of Treg immunoregulatory function — the approach avoids broad immune activation while delivering durable functional improvement, they wrote.
Although these findings represent a proof of principle rather than definitive clinical validation, researchers said it introduced a promising new direction for treating allergic asthma and potentially other immune‑mediated diseases characterized by Treg dysfunction.
The study’s authors encouraged future studies to confirm safety, durability and effectiveness in clinical settings as well as to determine whether Dectin‑1 expression could serve as a biomarker for patient stratification.
