Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses.
The mobilization of Langerhans cells (LCs) from epithelia to the draining lymph nodes is an essential process to initiate primary immune responses. We have recently shown that in mice, PGD2 is a potent inhibitor of epidermal LC emigration. In this study, we demonstrate that activation of the D prostanoid receptor 1 (DP1) impedes the TNF-alpha-induced migration of human LCs from skin explants and strongly inhibits the chemotactic responses of human LC precursors and of maturing LCs to CC chemokine ligands 20 and 19, respectively. Using a murine model of atopic dermatitis, a chronic Th2-type allergic inflammatory disease, we demonstrate that the potent DP1 agonist BW245C dramatically decreases the Ag-specific T cell activation in the skin draining lymph nodes and markedly prevents the skin lesions following repeated epicutaneous sensitization with OVA. Interestingly, analysis of the local response indicates that BW245C treatment strongly reduces the recruitment of inflammatory cells into the dermis and disrupts the Th1/Th2 balance, probably through the increased production of the immunoregulatory cytokine IL-10, in the skin of sensitized mice. Taken together, our results suggest a new function for DP1 in the regulation of the immune and inflammatory responses. We propose that DP1 activation by specific agonists may represent a strategy to control cutaneous inflammatory Th2-associated diseases.
Unité 547, Institut National de la Santé et de la Recherche Médicale, Institut Fédératif de Recherche 17, Institut Pasteur de Lille, Lille, France.
Véronique
V
Angeli
Delphine
D
Staumont
Anne-Sophie
AS
Charbonnier
Hamida
H
Hammad
Philippe
P
Gosset
Muriel
M
Pichavant
Bart N
BN
Lambrecht
Monique
M
Capron
David
D
Dombrowicz
François
F
Trottein
D000276:Adjuvants, Immunologic / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D046508:Culture Techniques; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015230:Prostaglandin D2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D010047:Ovalbumin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor