Table 1 Antigen presenting cell targets
From: Treatment of allergic asthma: Modulation of Th2 cells and their responses
Cell type | Target | Intervention example | Mechanism of action and effects | Comments |
|---|---|---|---|---|
Dendritic cell | Peroxisome proliferator-activated receptor gamma | Rosiglitazone and ciglitazone | Decrease CCR7 expression on DCs and diminishes migration [144, 145] | - |
| Â | Sphingosine 1-phosphate inhibitor | FTY720 | Sequesters lymphocytes in secondary lymphoid organs; inhibits T cell migration to the draining lymph nodes [146-;] suppresses eosinophilic airway inflammation and AHR, reduced Th2 cell generation [147, 148], generalised immunosuppression [149] | In clinical study for moderate asthma (ClinicalTrials.gov identifier: NCT00785083) |
| Â | Thymic stromal lymphopoietin (TSLP) | Anti-TSLP antibodies [39] | TSLP skews DCs to express high levels of OX40 ligand, which promotes the generation of Th2 cells [38]; its inhibition prevents Th2-mediated airway inflammation in mice [39] | - |
| Â | CCL2 | CCR2 antagonists [150] | Overexpressed in lung and increased DC recruitment in allergic asthma [151, 152] | CCR2 is involved in migration of other immune cells as well |
| Â | CD80/86 costimulation | D prostanoid 1 receptor agonist [153], aerosolised CD86 antisense oligonucleotide [154] or suplatast tosilate [155], | Reduce allergic disease in mice models of acute asthma | CD80/86 co-stimulation does not contribute to recall responses of effector Th2 cells [156] and might not be useful for the treatment of established disease |
| Â | OX40L | Anti-OX40L Ab | Blocks Th2 cell infiltration, cytokine secretion, IgE production and Th2 inflammation in mouse and non-human primate models [157] | - |
| Â | Programmed death-1 (PD-1) and PD1 ligands | None so far | PD-1 and its ligands regulate T cell activation and differentiation and affect asthmatic responses [158] | - |
Macrophage | Anti-A1 adenosine receptors | A1 adenosine receptor modulators | Anti-inflammatory [159] | Gene expression and function depends on polarisation (classical vs. alternative activation) [160] |
| Â | Unknown | Water-soluble chitosan | Suppresses allergic asthma in mice [161] | Â |
| Â | Unknown | Mycolic acid | Modulates airway macrophage function to suppress allergic inflammation in mice [162] | Â |
Basophil | Specific target unknown so far | N/A | CD49b+FcεR+ basophils migrate from blood to lymph nodes, where they present processed antigen to T cells in the context of MHC class II molecules and induce Th2 type polarisation through secretion of IL-4 [163–166] | Recently, the role of basophils in Th2 immunity was disputed in favour of inflammatory DCs [167, 168] |