Abstract
Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcεRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance.
Highlights
Allergen-specific immunotherapy (AIT) is the only cure for allergic diseases
While only the CD123+ dendritic cells (DC) subset frequency was affected after 1 year of treatment, expression of Fc receptor (FcR) and Ctype lectin receptors (CLR) was altered on several DC subsets
These modifications suggest an altered capacity of DC subsets to interact with allergens during AIT, which may represent cellular events linked to the protective effect of the treatment
Summary
Allergen-specific immunotherapy (AIT) is the only cure for allergic diseases. On repeated administration of hyposensitizing allergens, the immune reaction shifts from a Th2 profile towards a tolerogenic response. As reviewed by Akdis et al [1], effects induced by AIT include e.g. generation of regulatory T-cells and B-cells as well as increased levels of allergen-specific. AIT Alters the Frequency and FcR and CLR Profiles of DCs. IgG4 [1,2]. The full underlying mechanisms responsible for immune cell alterations associated with AIT remain elusive
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