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Mechanisms of allergen-specific immunotherapy and allergen tolerance

Kucuksezer, Umut C., Ozdemir, Cevdet, Cevhertas, Lacin, Ogulur, Ismail, Akdis, Mubeccel, Akdis, Cezmi A.·2020·Allergology International
DOI 10.1016/j.alit.2020.08.002
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Fig. 1 Launch of an allergic response. Allergic immune responses are initiated with uptake and processing of allergens by dendritic cells, the professional antigen presenting cells. Processed allergen peptides are presented to naïve CD4 þ Tcells that are differentiated to Th2 cells, with the presence of IL-4 in the micro milieu. Th2 cells produce the Th2 cytokines; IL-4, IL-5, IL-9 and IL-13. B cells consequently produce IgE which in turn binds to speci fi c Fc ε receptors on basophils and eosinophils; the effector cells of allergic in fl ammation. This event is called as sensitization. Upon recurrent encounter with the same allergen, immediate degranulation of these effector cells leads to discharge and production of histamine and leukotrienes, all of which lead to instant hypersensitivity reactions. Along with other functions in allergic in fl ammation, IL-4 acts in an autocrine manner for induction of CD4 þ Th2 cells. IL-5 contributes to activation, recruitment and survival of eosinophils. IL-9 induces increased mucus production while IL-13 and eosinophil products like major basic protein can induce epithelial damage and barrier leakiness. ILC2 contributes to allergic in fl ammation by production of Th2-type cytokines. The cytokines produced by epithelium; IL-25, IL-33 and TSLP can also be produced by Th2 cells and have capacity to activate ILC2. IL-25 induces DC activation. (BASO, Basophils; DC, Dendritic cells; EOS, Eosinophils; ILC, Innate lymphoid cells; LT, Leukotriene; MBP, Major basic protein; Th2, T helper type 2 cells; TSLP, Thymic stromal lymphopoietin.)
Fig. 1 Launch of an allergic response. Allergic immune responses are initiated with uptake and processing of allergens by dendritic cells, the professional antigen presenting cells. Processed allergen peptides are presented to naïve CD4 þ Tcells that are differentiated to Th2 cells, with the presence of IL-4 in the micro milieu. Th2 cells produce the Th2 cytokines; IL-4, IL-5, IL-9 and IL-13. B cells consequently produce IgE which in turn binds to speci fi c Fc ε receptors on basophils and eosinophils; the effector cells of allergic in fl ammation. This event is called as sensitization. Upon recurrent encounter with the same allergen, immediate degranulation of these effector cells leads to discharge and production of histamine and leukotrienes, all of which lead to instant hypersensitivity reactions. Along with other functions in allergic in fl ammation, IL-4 acts in an autocrine manner for induction of CD4 þ Th2 cells. IL-5 contributes to activation, recruitment and survival of eosinophils. IL-9 induces increased mucus production while IL-13 and eosinophil products like major basic protein can induce epithelial damage and barrier leakiness. ILC2 contributes to allergic in fl ammation by production of Th2-type cytokines. The cytokines produced by epithelium; IL-25, IL-33 and TSLP can also be produced by Th2 cells and have capacity to activate ILC2. IL-25 induces DC activation. (BASO, Basophils; DC, Dendritic cells; EOS, Eosinophils; ILC, Innate lymphoid cells; LT, Leukotriene; MBP, Major basic protein; Th2, T helper type 2 cells; TSLP, Thymic stromal lymphopoietin.)CC-BY-NC-ND · From the PDF
Fig. 2 Regulation of allergic immune responses following AIT. Allergen-speci fi c CD4 þ Treg cells are induced either as a consequence of a successful AIT or following high dose allergen exposure. Treg cells have capacity to produce the regulatory cytokines; IL-10, TGFb and IL-35 and also express surface molecules such as CTLA-4 and PD-1, all of which contribute to immune suppression of allergic responses. Treg cells suppress Th2 cells, eosinophils, basophils and can also induce allergen-speci fi c Breg cells. The suppressive milieu restricts IgE production while inducing production of IgG4 from B cells. Subsets of B cells, NK cells and ILCs with regulatory properties contribute to generation and conservation of allergen-speci fi c tolerance. (BAS, Basophils; EOS, Eosinophils; ILCreg, Regulatory innate lymphoid cells; NKreg, Regulatory natural killer cells; Treg, Regulatory T cells.)
Fig. 2 Regulation of allergic immune responses following AIT. Allergen-speci fi c CD4 þ Treg cells are induced either as a consequence of a successful AIT or following high dose allergen exposure. Treg cells have capacity to produce the regulatory cytokines; IL-10, TGFb and IL-35 and also express surface molecules such as CTLA-4 and PD-1, all of which contribute to immune suppression of allergic responses. Treg cells suppress Th2 cells, eosinophils, basophils and can also induce allergen-speci fi c Breg cells. The suppressive milieu restricts IgE production while inducing production of IgG4 from B cells. Subsets of B cells, NK cells and ILCs with regulatory properties contribute to generation and conservation of allergen-speci fi c tolerance. (BAS, Basophils; EOS, Eosinophils; ILCreg, Regulatory innate lymphoid cells; NKreg, Regulatory natural killer cells; Treg, Regulatory T cells.)CC-BY-NC-ND · From the PDF
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Metadata

Authors
Kucuksezer, U. C., Ozdemir, C., Cevhertas, L., Ogulur, I., Akdis, M., & Akdis, C. A.
ORCID
Kucuksezer, Umut C.
Venue
Allergology International
Publisher
Elsevier BV
Published
2020-10
Volume
69
Issue
4
Pages
549-560
ISSN
1323-8930
DOI
10.1016/j.alit.2020.08.002
Cited by
173
References
3
Language
en
Licence

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