Allergen-Specific Immunotherapy Alters the Frequency, as well as the FcR and CLR Expression Profiles of Human Dendritic Cell Subsets

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.

CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion

“…Thereby, we found a selective CLEC10A protein expression on human CD1c + DCs. While protein expression of CLEC10A on a human subpopulation of blood CD1c + DCs was already reported by Lundberg et al ( 53 , 54 ), we here show that CLEC10A is expressed on the majority of blood as well as lymphoid tissue CD1c + DCs. In contrast to Lundberg et al, we demonstrate that CLEC10A is specifically expressed on CD1c + DCs, but not on CD141 + DCs.…”

Mechanisms of allergen-specific immunotherapy

“…3,76 Several other studies have confirmed the impact of AIT on blood DCs. 77 Therefore, changes in molecular markers associated with DC2 and DCreg cells, reflecting the pro-allergic/regulatory response balance in peripheral blood, could be used as a potential biomarker of AIT efficacy and the acquisition of tolerance.…”

FcεRI expression and IgE binding by dendritic cells and basophils in allergic rhinitis and upon allergen immunotherapy

“…To our knowledge, this has not been reported before. One study reported a significant increase in FceRI expression on pDCs, but only after 1 year of AIT and not in parallel with changes in serum IgE 62. AIT-induced increases of serum IgE are generally modest compared to the sharp drop in free IgE levels seen upon treatment with omalizumab.…”