Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy

Pamela A. Frischmeyer-Guerrerio, Corinne A. Keet, Anthony L. Guerrerio, Kristin L. Chichester, Anja P. Bieneman, Robert G. Hamilton, Robert A. Wood, John T. Schroeder

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)47-59
Number of pages13
JournalClinical Immunology
Volume155
Issue number1
DOIs
StatePublished - Aug 19 2014

Keywords

  • Adaptive immunity
  • Dendritic cell
  • Food allergy
  • Immunotherapy
  • Innate immunity
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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