1. Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance 
Margot Berings, MD, Cagatay Karaaslan, PhD, Can Altunbulakli, MSc, Philippe Gevaert, MD, PhD, Mübeccel Akdis, MD, PhD, Claus Bachert, MD, PhD, Cezmi A. Akdis, MD 
Journal of Allergy and Clinical Immunology 
Volume 140, Issue 5, Pages (November 2017)
DOI: /j.jaci
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2. Fig 1
Cellular mechanisms of allergen-specific immunotherapy. Immune tolerance inducing conditioning and allergen uptake of regulatory DCs induces Treg and Breg cells. Allergen-specific regulatory cells induce tolerance to allergen in the periphery, and this suppressive environment regulates the effector cells of allergy. IL-10 and TGF-β production from Treg cells suppresses TH2 cell proliferation and TH2 cytokines while inducing IgG4 and IL-10 from allergen-specific B cells. Absence of TH2 cytokines in turn decreases basophil activation and mast cell, eosinophil, and ILC2 activity. HR2, Histamine receptor H2; IL10R, IL-10 receptor; PD1, programmed cell death protein 1; sCTLA4, soluble cytotoxic T lymphocyte–associated antigen 4; TGFβR, TGF-β receptor.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3. Fig 2
Mechanism of effect for mannan-conjugated allergoid vaccines in allergen-specific immunotherapy. The allergen of interest is polymerized and then glycoconjugated with mannan residues for synthesis of allergoids for vaccine use. Mannan receptor and DC-SIGN molecules expressed on human DCs facilitate uptake of allergoids and skew DCs to a regulatory phenotype. IL-10 secretion, together with presentation of allergoid-derived peptides, drives the allergen-specific naive T-cell pool into differentiation as Treg cells. PDL1 on DCs plays an important role in this context.83
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4. Fig 3
Mechanism of effect for retinoic acid supplementation in allergen-specific immunotherapy. Retinoic acid and LPS-pulsed human DCs together with uptake of allergen become retinoic acid–skewed dendritic cells (DC-RA). These DCs with a regulatory phenotype are capable of secreting IL-10, TGF-β, and IL-27. IL-10 and TGF-β in turn suppress proliferation and cytokine secretion from TH2 cells, whereas IL-27 drives TH2 and naive T cells to differentiate as Treg cells, establishing tolerance to allergen in the periphery.
Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci )
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions