Table 2.
Strategies to inhibit Th2 cell differentiation
| Target | Mechanism | Intervention example | Effect | Comment |
|---|---|---|---|---|
| GATA-3 | Development of Th2 cells [169] | Local treatment with GATA-3 antisense oligonucleotides [170] or RNA interference delivered by a lentiviral vector [171] | Inhibits allergen-induced asthma | Important for T cell development, its inhibition could cause immunosuppression [169] |
| STAT3 | Important for differentiation of Th2 cells [172] | Selective small molecule inhibitors [173] | Inhibits allergen-induced asthma | - |
| STAT5a | Important for differentiation of Th2 cells | None known | STAT-5a deficient mice have decreased IL-5 production and Th2 and eosinophil recruitment in mouse model of asthma [174] | Also important for development of inducible Tregs [175] |
| STAT6 | Important for differentiation of Th2 cells | Selective small molecule inhibitors [176] or RNA interference [177] of STAT6 | Suppresses Th2 responses in vitro and in animal models | - |
| Notch | Binds to the promoter of GATA-3 and regulates its transcription [178,179] | Gamma-secretase inhibitor (GSI) [180] | Selective inhibition of Th2, but not Th1 responses [181] | Involved in development of many other leukocytes and organs [182,183] |
| c-Maf | Transcription factor expressed at high levels in Th2 cells [184,185] | So-Cheong-Ryong-Tang (a Korean traditional medicine; [186]) or KR62890 (agonist of peroxisome proliferator-activated receptor γ; [187]) | Inhibits Th2 cell functions | Inhibits Th-17 and Treg function |
| Gfi-1, Dec2, ROG and Bcl-6 | Transcription repressors important for Th2 cell development [188-192] | None known | N/A | - |
| SOCS-3 | Inhibitor of cytokine signalling pathways [193] | None known | SOCS-3 blocks Th1 cell development and is preferentially expressed in Th2 cells [194] | Appears to be involved in Treg and/or Th17 cell development [195] |
| SOCS-5 | Inhibitor of cytokine signalling pathways [193] | None known | Preferentially expressed in Th1 cells and prevents Th2 cell development [196] | Its over-expression in T cells enhances airway inflammation and AHR [197] |
| miRNA-16, miRNA-21, miRNA-126 | Up-regulated in lung tissue after allergen challenge in mouse models of asthma [198,199] | Anti-miRNA-126 antagomir (small synthetic RNA molecule with modified backbone for degradation prevention) [199] | Prevents allergen-induced airway hyperreactivity and reduces allergic inflammation | - |