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Airway activation of formyl peptide receptors inhibits Th1 and Th17 cell responses via inhibition of mediator release from immune and inflammatory cells and maturation of dendritic cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Feb 15; Vol. 188 (4), pp. 1799-808. Date of Electronic Publication: 2012 Jan 18. - Publication Year :
- 2012
-
Abstract
- Formyl peptide receptors (FPRs) are chemoattractant receptors that mediate inflammatory cell responses to infection. Recent evidence indicates that noneosinophilic asthma phenotypes can be developed by both Th1 and Th17 cell responses when exposed to LPS-containing allergens. In this study, we evaluated the effects of airway activation of FPRs by their synthetic agonist, Trp-Lys-Tyr-Met-Val-D-Met (W-peptide), on the development of Th1 and Th17 cell responses in a noneosinophilic asthma mouse model. A noneosinophilic asthma mouse model was generated by intranasal sensitization with 10 μg of LPS plus 75 μg of OVA on days 0, 1, 2, and 7. Mice were then challenged with 50 μg of OVA alone on days 14, 15, 21, and 22. W-peptide was administered during the sensitization period, and immune and inflammatory responses were evaluated after OVA challenge. Lung inflammation after OVA challenge was partly abolished by airway activation of FPRs during sensitization. Maturation of dendritic cells (DCs) and migration of DCs from the lung to lung-draining lymph nodes were inhibited by FPR activation. In addition, airway activation of FPRs inhibited allergen-specific T cell proliferation in the lymph nodes. Production of IL-12 and IL-6 (Th1- and Th17-polarizing cytokines) from lung DCs was decreased by airway activation of FPRs. This effect resulted in the inhibition of allergen-specific Th1 and Th17 cell responses. Airway activation of FPRs during sensitization effectively prevents the development of Th1 and Th17 cell responses induced by LPS-containing allergens via multiple mechanisms, such as inhibition of DC maturation and migration and the production of Th1- and Th7-polarizing cytokines.
- Subjects :
- Animals
Asthma metabolism
Asthma pathology
Cell Differentiation drug effects
Cell Movement drug effects
Cell Proliferation drug effects
Dendritic Cells drug effects
Disease Models, Animal
Interleukin-12 biosynthesis
Interleukin-6 biosynthesis
Lung metabolism
Lung pathology
Lymph Nodes immunology
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Oligopeptides administration & dosage
Oligopeptides pharmacology
Ovalbumin immunology
Receptors, Formyl Peptide biosynthesis
Th1 Cells drug effects
Th17 Cells drug effects
Asthma immunology
Dendritic Cells immunology
Lung immunology
Receptors, Formyl Peptide metabolism
Th1 Cells immunology
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 188
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22262660
- Full Text :
- https://doi.org/10.4049/jimmunol.1102481