γδT17/γδTreg cell subsets: a new paradigm for asthma treatment

Abstract

Bronchial asthma (abbreviated as asthma)， is a heterogeneous disease characterized by chronic airway inflammation and airway hyperresponsiveness. The main characteristics of asthma include variable reversible airflow limitation and airway remodeling. The pathogenesis of asthma is still unclear. Th1/Th2 imbalance, Th1 deficiency and Th2 hyperfunction are classic pathophysiological mechanisms of asthma. Some studies have shown that the imbalance of the Th1/Th2 cellular immune model and Th17/Treg imbalance play a key role in the occurrence and development of asthma; however, these imbalances do not fully explain the disease. In recent years, studies have shown that γδT and γδT17 cells are involved in the pathogenesis of asthma. γδTreg has a potential immunosuppressive function, but its regulatory mechanisms have not been fully elucidated. In this paper, we reviewed the role of γδT17/γδTreg cells in bronchial asthma, including the mechanisms of their development and activation. Here we propose that γδT17/Treg cell subsets contribute to the occurrence and development of asthma, constituting a novel potential target for asthma treatment.

γδ T cells: origin and fate, subsets, diseases and immunotherapy

“…Another less well-characterized functional subset of γδ T cells that carries out regulatory functions in cancer or inflammatory diseases has been identified as γδTreg. [306][307][308][309][310][311] This population is induced upon receiving Inflammatory signals in the TME and could potentially sabotage the anti-tumor phenotype of γδ T cells while reprogramming them into γδTreg. 306,307,312 This subset has been identified as CD73 + Foxp3 + Vδ1 + T cell in the PBMC or tumor specimen of breast cancer patients 313 and tumorinfiltrated CD39 + Foxp3 + γδT in colon cancer.…”

“…7,20 In infections, they actively participate in pathogen clearance by producing IL-17, IFN-γ, and other proinflammatory cytokines, while activating immune cells such as macrophages and neutrophils. 57,59,346 However, dysregulated activation of γδT17 cells can lead to tissue damage 71,347 and chronic inflammation, 309 even autoimmune diseases like psoriasis. 69,313,348 Understanding their intricate regulation network is important for developing effective treatment regiments.…”

“…Notably, emerging research suggests that effector γδ T cells can transition into γδTreg under specific microenvironmental conditions. [306][307][308][309][310][311] Previously, we had thoroughly reviewed the regulatory functions of γδ T cells, 349,350 particularly Vδ1 and Vδ2 subsets, it was demonstrated that these subsets can be induced to express FoxP3 and execute regulatory functions in the presence of TGF-β, IL-2, and IL-15. 351 Similar to conventional Tregs, human γδ T cells employ various molecules such as GM-CSF, IL-10, TGF-β, IL-17, CD39, CD73, and checkpoint receptors as part of their immunosuppressive mechanisms.…”

Regulatory T cells in lung disease and transplantation

“…Yao et al found that the suppressive function and stability of Treg cells are enhanced by androgen receptor signaling, which down-regulates ST2 expression on Treg cells and reduces allergen-induced IL-33 expression in airway epithelial cells. In addition, Treg cells were demonstrated to improve airway remodeling and restore Th1/Th2 balance through the DLL4-Notch signaling pathway [ 160 , 161 ].…”

Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

“…Typically, asthma is characterized by two major predominant phenotypes: eosinophilic vs. neutrophilic and T helper type 1 (Th1) vs. Th2, or even mixed eosinophilic/neutrophilic inflammatory patterns [ 27 , 31 ]. However, newer variants of the T-cell immune response, such as T helper type 9 (Th9), T helper type 17 (Th17) and T helper type 22 (Th22), have also been shown to contribute to immune cell responses in asthma [ 32 , 33 ]. Eosinophilic inflammation can be associated with the spectrum of asthma severity, ranging from mild to moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs typically in more severe asthma [ 34 , 35 ].…”