title: 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.
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.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology Biotech Center, Pohang 790-784, Republic of Korea.
authors.forename: You-Me
authors.initials: YM
authors.lastname: Tae
authors.forename: Hyun Taek
authors.initials: HT
authors.lastname: Park
authors.forename: Hyung-Geun
authors.initials: HG
authors.lastname: Moon
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Hyouk-Soo
authors.initials: HS
authors.lastname: Kwon
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D044042:Receptors, Formyl Peptide / Q000096:biosynthesis / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; C113617:Trp-Lys-Tyr-Met-Val-Met; D018664:Interleukin-12; D010047:Ovalbumin