Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1.
PGD(2) is the major mediator released by mast cells during allergic responses, and it acts through two different receptors, the D prostanoid receptor 1 (DP1) and DP2, also known as CRTH2. Recently, it has been shown that PGD(2) inhibits the migration of epidermal Langerhans cells to the skin draining lymph nodes (LNs) and affects the subsequent cutaneous inflammatory reaction. However, the role of PGD(2) in the pulmonary immune response remains unclear. Here, we show that the intratracheal instillation of FITC-OVA together with PGD(2) inhibits the migration of FITC(+) lung DC to draining LNs. This process is mimicked by the DP1 agonist BW245C, but not by the DP2 agonist DK-PGD(2). The ligation of DP1 inhibits the migration of FITC-OVA(+) DCs only temporarily, but still inhibits the proliferation of adoptively transferred, OVA-specific, CFSE-labeled, naive T cells in draining LNs. These T cells produced lower amounts of the T cell cytokines IL-4, IL-10, and IFN-gamma compared with T cells from mice that received FITC-OVA alone. Taken together, our data suggest that the activation of DP receptor by PGD(2) may represent a pathway to control airway DC migration and to limit the activation of T cells in the LNs under steady state conditions, possibly contributing to homeostasis in the lung.
Hammad
Hamida
H
Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. h.hammad@erasmusmc.nl
de Heer
Hendrik Jan
HJ
Soullie
Thomas
T
Hoogsteden
Henk C
HC
Trottein
Francois
F
Lambrecht
Bart N
BN
D000818:Animals; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D006827:Hydantoins / Q000008:administration & dosage; D007442:Intubation, Intratracheal; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015230:Prostaglandin D2 / Q000008:administration & dosage* / Q000378:metabolism; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013909:Thorax
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006827:Hydantoins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C030669:BW 245C; D010047:Ovalbumin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor