[en] The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced during inflammatory reactions, is involved in the control of immune responses, its effect on the differentiation and functions of human monocyte-derived dendritic cells (MDDC) was studied. We show that DC differentiated in the presence of PGD(2) (PG/DC) have an unusual phenotype, with modifications in the expression of molecules involved in antigen (Ag) capture and presentation, leading to higher endocytic and Ag-processing activities. However, under conditions that necessitated Ag processing and presentation, PG/DC have an impaired ability to stimulate naive T cells, whereas superAg-pulsed DC efficiently promote their proliferation. Upon lipopolysaccharide or TNF-alpha/IL-1beta stimulation, PG/DC phenotypically mature but produce abnormal amounts of immunoregulatory cytokines (decreased IL-12p70/IL-10 ratio). Moreover, mature PG/DC fail to up-regulate the chemokine receptor CCR7 and show an impaired migration towards its ligand CCL19. Finally, PG/DC favor the differentiation of naive T cells toward Th2 cells, an effect dependent on IL-10 and inducible costimulator ligand expression by DC. Most of the herein described effects of PGD(2) on MDDC can be reproduced, usually with a higher efficacy, with a selective D prostanoid receptor (DP)1, but not DP2, agonist. Taken as a whole, these results demonstrate that PGD(2) impacts DC differentiation and functions, and extend the concept that it exerts important roles in immunity
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Gosset, Philippe
Pichavant, Muriel
Faveeuw, Christelle
Bureau, Fabrice ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Tonnel, Andre-Bernard
Trottein, Francois
Language :
English
Title :
Prostaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response.
Banchereau, J. and Steinman, R. M., Dendritic cells and the control of immunity. Nature 1998. 392: 245-252.
Steinman, R. M., Pack, M. and Inaba, K., Dendritic cells in the T cell areas of lymphoid organs. Immunol. Rev. 1997. 156: 25-37.
Cella, M., Sallusto, F. and Lanzavecchia, A., Origin, maturation and antigen presenting function of dendritic cells. Curr. Opin. Immunol. 1997. 9: 10-16.
Bousquet, J., Jeffery, P. K., Busse, W. W., Johnson, M. and Vignola, A. M., Asthma. From bronchoconstriction to airways inflammation and remodeling. Am. J. Respir. Crit. Care Med. 2000. 161: 1720-1745.
Lambrecht, B. N., De Veerman, M., Coyle, A. J., Gutierrez-Ramos, J. C., Thielemans, K. and Pauwels, R. A., Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J. Clin. Invest. 2000. 106: 551-559.
Moller, G. M., Overbeek, S. E., Van Helden-Meeuwsen, C. G., Van Haarst, J. M., Prens, E. P., Mulder, P. G., Postma, D. S. and Hoogsteden, H. C., Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin. Exp. Allergy 1996. 26: 517-524.
Hammad, H., Lambrecht, B. N., Pochard, P., Gosset, P., Marquillies, P., Tonnel, A. B. and Pestel, J., Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: involvement of CCR7. J. Immunol. 2002. 169: 1524-1534.
Caron, G., Delneste, Y., Roelandts, E., Duez, C., Bonnefoy, J. Y., Pestel, J. and Jeannin, P., Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells. J. Immunol. 2001. 167: 3682-3686.
Angeli, V., Faveeuw, C., Roye, O., Fontaine, J., Teissier, E., Capron, A., Wolowczuk, I., Capron, M. and Trottein, F., Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J. Exp. Med. 2001. 193: 1135-1147.
Faveeuw, C., Gosset, P., Bureau, F., Angeli, V., Hirai, H., Maruyama, T., Narumiya, S., Capron, M. and Trottein, F., Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways. Eur. J. Immunol. 2003. 33: 889-898.
Gosset, P., Bureau, F., Angeli, V., Pichavant, M., Faveeuw, C., Tonnel, A. B. and Trottein, F., Prostaglandin D2 affects the maturation of human monocyte-derived dendritic cells: consequence on the polarization of naive Th cells. J. Immunol. 2003. 170: 4943-4952.
Narumiya, S. and FitzGerald, G. A., Genetic and pharmacological analysis of prostanoid receptor function. J. Clin. Invest. 2001. 108: 25-30.
Hirai, H., Tanaka, K., Yoshie, O., Ogawa, K., Kenmotsu, K., Takamori, Y., Ichimasa, M., Sugamura, K., Nakamura, M., Takano, S. and Nagata, K., Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J. Exp. Med. 2001. 193: 255-261.
Hammad, H., de Heer, H. J., Soullie, T., Hoogsteden, H. C., Trottein, F. and Lambrecht, B. N., Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1. J. Immunol. 2003. 171: 3936-3940.
Angeli, V., Staumont, D., Charbonnier, A. S., Hammad, H., Gosset, P., Pichavant, M., Lambrecht, B. N., Capron, M., Dombrowicz, D. and Trottein, F., Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses. J. Immunol. 2004. 172: 3822-3829.
Steinbrink, K., Paragnik, L., Jonuleit, H., Tuting, T., Knop, J. and Enk, A. H., Induction of dendritic cell maturation and modulation of dendritic cell-induced immune responses by prostaglandins. Arch. Dermatol. Res. 2000. 292: 437-445.
Kliewer, S. A., Lenhard, J. M., Willson, T. M., Patel, I., Morris, D. C. and Lehmann, J. M., A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 1995. 83: 813-819.
Gosset, P., Charbonnier, A. S., Delerive, P., Fontaine, J., Staels, B., Pestel, J., Tonnel, A. B. and Trottein, F., Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells. Eur. J. Immunol. 2001. 31: 2857-2865.
Nencioni, A., Grunebach, F., Zobywlaski, A., Denzlinger, C., Brugger, W. and Brossart, P., Dendritic cell immunogenicity is regulated by peroxisome proliferator activated receptor gamma. J. Immunol. 2002. 169: 1228-1235.
Mohty, M., Morbelli, S., Isnardon, D., Sainty, D., Arnoulet, C., Gaugler, B. and Olive, D., All-trans retinoic acid skews monocyte differentiation into interleukin-12-secreting dendritic-like cells. Br. J. Haematol. 2003. 122: 829-836.
Mohty, M., Vialle-Castellano, A., Nunes, J. A., Isnardon, D., Olive, D. and Gaugler, B., IFN-alpha skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities. J. Immunol. 2003. 171: 3385-3393.
Rissoan, M. C., Soumelis, V., Kadowaki, N., Grouard, G., Briere, F., de Waal Malefyt, R. and Liu, Y. J., Reciprocal control of T helper cell and dendritic cell differentiation. Science 1999. 283: 1183-1186.
Ebner, S., Hofer, S., Nguyen, V. A., Furhapter, C., Herold, M., Fritsch, P., Heufler, C. and Romani, N., A novel role for IL-3: human monocytes cultured in the presence of IL-3 and IL-4 differentiate into dendritic cells that produce less IL-12 and shift Th cell responses toward a Th2 cytokine pattern. J. Immunol. 2002. 168: 6199-6207.
Kalinski, P., Hilkens, C. M., Snijders, A., Snijdewint, F. G. and Kapsenberg, M. L., IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J. Immunol. 1997. 159: 28-35.
Penna, G. and Adorini, L., 1α,25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 2000. 164: 2405-2411.
Yarilin, D., Duan, R., Huang, Y. M. and Xiao, B. G., Dendritic cells exposed in vitro to TGF-beta1 ameliorate experimental autoimmune myasthenia gravis. Clin. Exp. Immunol. 2002. 127: 214-219.
Boie, Y., Sawyer, N., Slipetz, D. M., Metters, K. M. and Abramovitz, M., Molecular cloning and characterization of the human prostanoid DP receptor. J. Biol. Chem. 1995. 270: 18910-18916.
Deslee, G., Charbonier, A. S., Hammad, H., Angyalosi, G., Tillie-Leblond, I., Mantovani, A., Tonnel, A. B. and Pestel, J., Involvement of the mannose receptor in the uptake of der p 1, a major mite allergen, by human dendritic cells. J. Allergy Clin. Immunol. 2002. 110: 763-770.
Santambrogio, L., Sato, A. K., Carven, G. J., Belyanskaya, S. L., Strominger, J. L. and Stern, L. J., Extracellular antigen processing and presentation by immature dendritic cells. Proc. Natl. Acad. Sci. USA 1999. 96: 15056-15061.
Akbari, O., Freeman, G. J., Meyer, E. H., Greenfield, E. A., Chang, T. T., Sharpe, A. H., Berry, G., DeKruyff, R. H. and Umetsu, D. T., Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat. Med. 2002. 8: 1024-1032.
Morelli, A. E. and Thomson, A. W., Dendritic cells under the spell of prostaglandins. Trends Immunol. 2003. 24: 108-111.
Murray, J. J., Tonnel, A. B., Brash, A. R., Roberts, L. J., 2nd, Gosset, P., Workman, R., Capron, A. and Oates, J. A., Release of prostaglandin D2 into human airways during acute antigen challenge. N. Engl. J. Med. 1986. 315: 800-804.
van Kooyk, Y. and Geijtenbeek, T. B., DC-SIGN: escape mechanism for pathogens. Nat. Rev. Immunol. 2003. 3: 697-709.
Vincent, M. S., Gumperz, J. E. and Brenner, M. B., Understanding the function of CD1-restricted T cells. Nat. Immunol. 2003. 4: 517-523.
Kronenberg, M. and Gapin, L., The unconventional lifestyle of NKT cells. Nat. Rev. Immunol. 2002. 2: 557-568.
Akbari, O., Stock, P., Meyer, E., Kronenberg, M., Sidobre, S., Nakayama, T., Taniguchi, M., Grusby, M. J., DeKruyff, R. H. and Umetsu, D. T., Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat. Med. 2003. 9: 582-588.
Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C. et al., Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat. Med. 2003. 9: 562-567.
Ohshima, Y., Yang, L. P., Uchiyama, T., Tanaka, Y., Baum, P., Sergerie, M., Hermann, P. and Delespesse, G., OX40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4(+) T cells into high IL-4-producing effectors. Blood 1998. 92: 3338-3345.
McAdam, A. J., Chang, T. T., Lumelsky, A. E., Greenfield, E. A., Boussiotis, V. A., Duke-Cohan, J. S., Chernova, T., Malenkovich, N., Jabs, C., Kuchroo, V. K. et al., Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells. J. Immunol. 2000. 165: 5035-5040.
Giordano, D., Magaletti, D. M., Clark, E. A. and Beavo, J. A., Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN(+) (CD209) intermediate cell and impair differentiation into dendritic cells. J. Immunol. 2003. 171: 6421-6430.
Saeki, H., Moore, A. M., Brown, M. J. and Hwang, S. T., Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J. Immunol. 1999. 162: 2472-2475.
Ujihara, M., Urade, Y., Eguchi, N., Hayashi, H., Ikai, K. and Hayaishi, O., Prostaglandin D2 formation and characterization of its synthetases in various tissues of adult rats. Arch. Biochem. Biophys. 1988. 260: 521-531.
Nithipatikom, K., Isbell, M. A., Lindholm, P. F., Kajdacsy-Balla, A., Kaul, S. and Campell, W. B., Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate cancer cell invasion. Clin. Exp. Metastasis 2002. 19: 593-601.