The α2A-adrenergic receptor on Tfh cells amplifies allergic airway inflammation via Akt signaling
4 affiliations
- 1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2Shanghai Key Laboratory of Severe Respiratory Infection, Shanghai, China
- 3Unit of Respiratory Infection and Immunity, Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- 4Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
Abstract
Allergic airway inflammation involves complex neuro‑immune interactions, yet the role of α2A‑adrenergic receptors (α2AR, encoded by Adra2a) in Tfh development and type 2 immunity remains poorly defined. HDM‑induced asthma model was established in C57BL/6 mice. RNA‑sequencing, correlation analysis, flowcytometry, immunofluorescence, and pharmacological interventions were used. Il33 knockout mice and T‑cell‑specific Adra2a or Akt1 knockout mice were generated. GEO datasets were analyzed for Tfh cell signatures. We found that HDM challenge significantly upregulated Adra2a in lung and lymph nodes. Adra2a expression was strongly correlated with type 2 chemokines Ccl11, Il33, and Ccl17. In Il33KO mice, Adra2a was among the top downregulated genes, and Il33 deletion broadly suppressed type 2 inflammation genes. Catecholamine‑metabolizing enzymes showed differential correlations: Maoa positively correlated with Adra2a and asthma genes, whereas Maob and Ddc were negatively correlated. α2AR was highly expressed on Tfh cells, especially on GC‑Tfh cells. α2AR activation aggravated airway inflammation, increased Tfh and germinal center B cells, promoted type 2 cytokines and IgE, and AKT phosphorylation. Conversely, T‑cell‑specific Adra2a knockout or Akt1 knockout attenuated these effects. α2AR is a key regulator linking neuro‑immune crosstalk to type 2 airway inflammation. It promotes Tfh cell differentiation and allergic responses via AKT signaling. Targeting α2AR may represent a novel therapeutic strategy for asthma.
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BibTeX
@article{lan2026α2aadrenergic,
title = {{The α2A-adrenergic receptor on Tfh cells amplifies allergic airway inflammation via Akt signaling}},
author = {Gelei Lan and Juan Du and Jie Chen and Shitao Xie and Xiaoyun Lai and Yue Zhao and Yahui Liu and Chunrong Huang and Xueqing Du and Yidan Sun and Guochao Shi and Xiao Su},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10670-6},
url = {https://doi.org/10.1038/s42003-026-10670-6},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The α2A-adrenergic receptor on Tfh cells amplifies allergic airway inflammation via Akt signaling
AU - Gelei Lan
AU - Juan Du
AU - Jie Chen
AU - Shitao Xie
AU - Xiaoyun Lai
AU - Yue Zhao
AU - Yahui Liu
AU - Chunrong Huang
AU - Xueqing Du
AU - Yidan Sun
AU - Guochao Shi
AU - Xiao Su
PY - 2026
DA - 2026/07/13
JO - Communications Biology
DO - 10.1038/s42003-026-10670-6
UR - https://doi.org/10.1038/s42003-026-10670-6
AB - Allergic airway inflammation involves complex neuro‑immune interactions, yet the role of α2A‑adrenergic receptors (α2AR, encoded by Adra2a) in Tfh development and type 2 immunity remains poorly defined. HDM‑induced asthma model was established in C57BL/6 mice. RNA‑sequencing, correlation analysis, flowcytometry, immunofluorescence, and pharmacological interventions were used. Il33 knockout mice and T‑cell‑specific Adra2a or Akt1 knockout mice were generated. GEO datasets were analyzed for Tfh cell signatures. We found that HDM challenge significantly upregulated Adra2a in lung and lymph nodes. Adra2a expression was strongly correlated with type 2 chemokines Ccl11, Il33, and Ccl17. In Il33KO mice, Adra2a was among the top downregulated genes, and Il33 deletion broadly suppressed type 2 inflammation genes. Catecholamine‑metabolizing enzymes showed differential correlations: Maoa positively correlated with Adra2a and asthma genes, whereas Maob and Ddc were negatively correlated. α2AR was highly expressed on Tfh cells, especially on GC‑Tfh cells. α2AR activation aggravated airway inflammation, increased Tfh and germinal center B cells, promoted type 2 cytokines and IgE, and AKT phosphorylation. Conversely, T‑cell‑specific Adra2a knockout or Akt1 knockout attenuated these effects. α2AR is a key regulator linking neuro‑immune crosstalk to type 2 airway inflammation. It promotes Tfh cell differentiation and allergic responses via AKT signaling. Targeting α2AR may represent a novel therapeutic strategy for asthma.
SN - 2399-3642
ER -