Table 1.
Stage of allergy | Cell subset | Key functional molecules | Role in allergic rhinitis | Effects of allergen immunotherapy |
---|---|---|---|---|
Sensitization | EC |
RNA GAS5 [35] |
DC recruitment [24•] Induction of ILC2 [29] and DC2 [27] cell subsets Promotion of TH2 [30] and inhibition of TH1 [35] polarization Promotion of mast cell degranulation [31] |
Restoration of EC integrity in murine models [81] |
DC2 |
MHC II CD80/CD86 [32] |
TH2 polarization Antigen presentation [32] |
Promotion of DCreg polarization [27, 82] Increased FcεRI expression [46•] |
|
TFH2 | Surface CD40 secreted IL-4, IL-13, IL-21 [36, 39] | Induction of B cell ε-germline transcription, differentiation and affinity maturation and sIgE production [39, 41] |
Decreased circulating numbers [38, 83] Restored function of suppressive counterparts TFR cells [84] |
|
B cells | IgE [42] |
Mast cell and basophil sensitization [42] Antigen presentation [85••] |
Induction of IgG+ B cells [39, 47, 86–88•] Induction of IL-10+Bregs [87–90] Reduced CD23 expression [85••] |
|
Early phase responses | Basophils | Histamine, tryptase, cysteinyl leukotrienes, PGD2 [43, 44, 50, 51] |
Promotion of TH2 polarization [33] Activation of ILC2s [51] Increasing vascular permeability and immune cell influx [50] Induction of symptoms: itching, sneezing, rhinorrhea [44] |
|
Mast cells | ||||
Late phase responses | TH2 | IL-4, IL-5, IL-9, IL-13 [44, 50, 64, 67, 99] |
Induction of B cell ε-germline transcription, differentiation and affinity maturation [41] Downregulation of tight junctions of nasal epithelium [50] Upregulation of endothelial adhesion molecules [61] Promotion of basophil and mast cell differentiation [67] |
Induction of iTregs [100–103] and nTregs [103–106] Reduced TH2 and increased TH1 frequencies and corresponding cytokines [100, 107–112] |
ILC2s | Reduced circulating frequencies [80, 113•] | |||
Eosinophils | LTC4, PGE2, EDN, ECP [66] | Damage of the nasal epithelium [65] | Reduced infiltration [92, 104, 107, 114, 115] | |
Neutrophils | MHC II [74] | Antigen presentation [74] | Reduced activation (157) |