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 language | English (US) |
|---|---|
| Pages (from-to) | 47-59 |
| Number of pages | 13 |
| Journal | Clinical Immunology |
| Volume | 155 |
| Issue number | 1 |
| DOIs | |
| State | Published - Aug 19 2014 |
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Keywords
- Adaptive immunity
- Dendritic cell
- Food allergy
- Immunotherapy
- Innate immunity
- Tolerance
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy. / Frischmeyer-Guerrerio, Pamela A.; Keet, Corinne; Guerrerio, Anthony L; Chichester, Kristin L.; Bieneman, Anja P.; Hamilton, Robert G; Wood, Robert A; Schroeder, John Thomas.
In: Clinical Immunology, Vol. 155, No. 1, 19.08.2014, p. 47-59.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy
AU - Frischmeyer-Guerrerio, Pamela A.
AU - Keet, Corinne
AU - Guerrerio, Anthony L
AU - Chichester, Kristin L.
AU - Bieneman, Anja P.
AU - Hamilton, Robert G
AU - Wood, Robert A
AU - Schroeder, John Thomas
PY - 2014/8/19
Y1 - 2014/8/19
N2 - 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.
AB - 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.
KW - Adaptive immunity
KW - Dendritic cell
KW - Food allergy
KW - Immunotherapy
KW - Innate immunity
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=84907166867&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907166867&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2014.08.006
DO - 10.1016/j.clim.2014.08.006
M3 - Article
C2 - 25173802
AN - SCOPUS:84907166867
VL - 155
SP - 47
EP - 59
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
IS - 1
ER -