title: 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.
authors: Department of Immunotechnology, Lund University, Lund, Sweden.
authors: Kristina
authors: K
authors: Lundberg
authors: Department of Immunotechnology, Lund University, Lund, Sweden.
authors: Frida
authors: F
authors: Rydnert
authors: Department of Immunotechnology, Lund University, Lund, Sweden.
authors: Sissela
authors: S
authors: Broos
authors: Department of Otorhinolaryngology, Head & Neck Surgery, Skåne University Hospital, Lund, Sweden.
authors: Morgan
authors: M
authors: Andersson
authors: Department of Otorhinolaryngology, Head & Neck Surgery, Skåne University Hospital, Lund, Sweden.
authors: Lennart
authors: L
authors: Greiff
authors: Department of Immunotechnology, Lund University, Lund, Sweden.
authors: Malin
authors: M
authors: Lindstedt
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000918:Antibody Specificity; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000032:analysis; D002452:Cell Count; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D003888:Desensitization, Immunologic; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D011961:Receptors, Fc / Q000096:biosynthesis* / Q000235:genetics; D018180:Thrombomodulin; D055815:Young Adult
chemical_list: D000485:Allergens; D000954:Antigens, Surface; C115022:IL3RA protein, human; D007074:Immunoglobulin G; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type; D011961:Receptors, Fc; C546931:THBD protein, human; D018180:Thrombomodulin; D007073:Immunoglobulin E