title: Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy.
abstract: Sublingual (SLIT) and oral immunotherapy (OIT) are promising treatments for food allergy, but underlying mechanisms are poorly understood. Dendritic cells (DCs) induce and maintain Th2-type allergen-specific T cells, and also regulate innate immunity through their expression of Toll-like receptors (TLRs). We examined how SLIT and OIT influenced DC innate and adaptive immune responses in children with IgE-mediated cow's milk (CM) allergy. SLIT, but not OIT, decreased TLR-induced IL-6 secretion by myeloid DCs (mDCs). SLIT and OIT altered mDC IL-10 secretion, a potent inhibitor of FcεRI-dependent pro-inflammatory responses. OIT uniquely augmented IFN-α and decreased IL-6 secretion by plasmacytoid DCs (pDCs), which was associated with reduced TLR-induced IL-13 release in pDC-T cell co-cultures. Both SLIT and OIT decreased Th2 cytokine secretion to CM in pDC-T, but not mDC-T, co-cultures. Therefore, SLIT and OIT exert unique effects on DC-driven innate and adaptive immune responses, which may inhibit allergic inflammation and promote tolerance.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: pguerrerio@jhmi.edu.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Frischmeyer-Guerrerio
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: ckeet1@jhmi.edu.
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Keet
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: aguerrerio@jhmi.edu.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Guerrerio
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: kchiches@jhmi.edu.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Chichester
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: abienema@jhmi.edu.
authors.forename: Anja P
authors.initials: AP
authors.lastname: Bieneman
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: rhamilto@jhmi.edu.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: rwood@jhmi.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wood
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: schray@jhmi.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Schroeder
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000293:Adolescent; D000485:Allergens / Q000008:administration & dosage* / Q000627:therapeutic use*; D002478:Cells, Cultured; D002648:Child; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells; D004311:Double-Blind Method; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016269:Milk Hypersensitivity / Q000628:therapy*; D010457:Peptidoglycan / Q000494:pharmacology; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D010457:Peptidoglycan; D017455:Receptors, IgE; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2
keywords: Adaptive immunity;; Dendritic cell;; Food allergy;; Immunotherapy;; Innate immunity;; Tolerance