{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:57:16Z","timestamp":1791205036752,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>PGI2, which exerts its actions via its specific Gs-coupled I prostanoid receptor (IP), is known to be present in the lymph nodes, but its roles in acquired cutaneous immune responses remain unclear. To investigate the role of PGI2\u2013IP signaling in cutaneous immune responses, we applied IP-deficient (Ptgir\u2212\/\u2212) mice to contact hypersensitivity as a model of acquired immune response and found that Ptgir\u2212\/\u2212 mice exhibited a significantly decreased contact hypersensitivity response. Lymph node cells from sensitized Ptgir\u2212\/\u2212 mice exhibited decreased IFN-\u03b3 production and a smaller T-bet+ subset compared with control mice. PGI synthase and IP expression were detected in dendritic cells and T cells, respectively, by quantitative real-time PCR analysis, suggesting that PGI2 produced by dendritic cells acts on IP in T cells. In fact, in vitro Th1 differentiation was enhanced by an IP agonist, and this enhancement was nullified by protein kinase A inhibitor. These results suggest that PGI2\u2013IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses.<\/jats:p>","DOI":"10.4049\/jimmunol.0903260","type":"journal-article","created":{"date-parts":[[2010,4,16]],"date-time":"2010-04-16T22:18:29Z","timestamp":1271456309000},"page":"5595-5603","source":"Crossref","is-referenced-by-count":63,"title":["Prostaglandin I2\u2013IP Signaling Promotes Th1 Differentiation in a Mouse Model of Contact Hypersensitivity"],"prefix":"10.1093","volume":"184","author":[{"given":"Saeko","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Dermatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiji","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyohei","family":"Egawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine , Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Tanizaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina Sagita","family":"Moniaga","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine , Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Miyachi","sequence":"additional","affiliation":[{"name":"Department of Dermatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuh","family":"Narumiya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kabashima","sequence":"additional","affiliation":[{"name":"Department of Dermatology"},{"name":"Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine , Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,15]]},"reference":[{"key":"2026012806273366000_r1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nri705","article-title":"T(H)1 and T(H)2 cells: a historical perspective.","volume":"2","author":"Liew","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2026012806273366000_r2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0167-5699(96)80606-2","article-title":"The expanding universe of T-cell subsets: Th1, Th2 and more.","volume":"17","author":"Mosmann","year":"1996","journal-title":"Immunol. Today"},{"key":"2026012806273366000_r3","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1146\/annurev.immunol.25.022106.141557","article-title":"IL-17 family cytokines and the expanding diversity of effector T cell lineages.","volume":"25","author":"Weaver","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"2026012806273366000_r4","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1002\/1521-4141(200108)31:8<2487::AID-IMMU2487>3.0.CO;2-L","article-title":"Weak TCR stimulation induces a calcium signal that triggers IL-4 synthesis, stronger TCR stimulation induces MAP kinases that control IFN-gamma production.","volume":"31","author":"Badou","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"2026012806273366000_r5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.immunol.15.1.297","article-title":"Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches.","volume":"15","author":"Constant","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"2026012806273366000_r6","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1146\/annurev.immunol.21.120601.140942","article-title":"Molecular mechanisms regulating Th1 immune responses.","volume":"21","author":"Szabo","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"2026012806273366000_r7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jdermsci.2003.11.008","article-title":"Prostanoids in the cutaneous immune response.","volume":"34","author":"Kabashima","year":"2004","journal-title":"J. Dermatol. Sci."},{"key":"2026012806273366000_r8","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s10156-008-0622-3","article-title":"The roles of prostanoids in infection and sickness behaviors.","volume":"14","author":"Matsuoka","year":"2008","journal-title":"J. Infect. Chemother."},{"key":"2026012806273366000_r9","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1152\/physrev.1999.79.4.1193","article-title":"Prostanoid receptors: structures, properties, and functions.","volume":"79","author":"Narumiya","year":"1999","journal-title":"Physiol. Rev."},{"key":"2026012806273366000_r10","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF00915791","article-title":"Regulation of the immune response by prostaglandins.","volume":"3","author":"Goodwin","year":"1983","journal-title":"J. Clin. Immunol."},{"key":"2026012806273366000_r11","doi-asserted-by":"crossref","first-page":"768","DOI":"10.4049\/jimmunol.131.2.768","article-title":"Analysis of the defects responsible for the impaired regulation of EBV-induced B cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin E.","volume":"131","author":"Hasler","year":"1983","journal-title":"J. Immunol."},{"key":"2026012806273366000_r12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4049\/jimmunol.146.1.108","article-title":"Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines.","volume":"146","author":"Betz","year":"1991","journal-title":"J. Immunol."},{"key":"2026012806273366000_r13","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1172\/JCI200113640","article-title":"Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse.","volume":"108","author":"Nataraj","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2026012806273366000_r14","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1172\/JCI0214459","article-title":"The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut.","volume":"109","author":"Kabashima","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2026012806273366000_r15","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1084\/jem.20070773","article-title":"Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1.","volume":"204","author":"Nagamachi","year":"2007","journal-title":"J. Exp. Med."},{"key":"2026012806273366000_r16","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nm.1968","article-title":"Prostaglandin E(2)-EP4 signaling promotes immune inflammation through T(H)1 cell differentiation and T(H)17 cell expansion.","volume":"15","author":"Yao","year":"2009","journal-title":"Nat Med."},{"key":"2026012806273366000_r17","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1016\/j.molimm.2007.01.025","article-title":"Prostacyclin production is not controlled by prostacyclin synthase but by cyclooxygenase-2 in a human follicular dendritic cell line, HK.","volume":"44","author":"Lee","year":"2007","journal-title":"Mol. Immunol."},{"key":"2026012806273366000_r18","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/j.1600-0625.2006.00480.x","article-title":"Time course changes of scratching counts, dermatitis symptoms, and levels of cutaneous prostaglandins in NC\/Nga mice.","volume":"15","author":"Sugimoto","year":"2006","journal-title":"Exp. Dermatol."},{"key":"2026012806273366000_r19","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.4049\/jimmunol.169.10.5997","article-title":"A key role for prostaglandin I2 in limiting lung mucosal Th2, but not Th1, responses to inhaled allergen.","volume":"169","author":"Jaffar","year":"2002","journal-title":"J. Immunol."},{"key":"2026012806273366000_r20","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1365-2125.1985.tb02671.x","article-title":"Lung function and plasma levels of thromboxane B2, 6-ketoprostaglandin F1 alpha and beta-thromboglobulin in antigen-induced asthma before and after indomethacin pretreatment.","volume":"19","author":"Shephard","year":"1985","journal-title":"Br. J. Clin. Pharmacol."},{"key":"2026012806273366000_r21","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1152\/jappl.1982.53.3.589","article-title":"Cyclooxygenase metabolites in human lung anaphylaxis: airway vs. parenchyma.","volume":"53","author":"Schulman","year":"1982","journal-title":"J. Appl. Physiol."},{"key":"2026012806273366000_r22","doi-asserted-by":"crossref","first-page":"9986","DOI":"10.1016\/S0021-9258(17)36979-X","article-title":"cDNA cloning of a mouse prostacyclin receptor. Multiple signaling pathways and expression in thymic medulla.","volume":"269","author":"Namba","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2026012806273366000_r23","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1189\/jlb.0606375","article-title":"Prostaglandin I2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells.","volume":"81","author":"Zhou","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"2026012806273366000_r24","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1172\/JCI28949","article-title":"Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function.","volume":"117","author":"Idzko","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2026012806273366000_r25","doi-asserted-by":"crossref","first-page":"6193","DOI":"10.4049\/jimmunol.179.9.6193","article-title":"Prostaglandin I2-IP signaling blocks allergic pulmonary inflammation by preventing recruitment of CD4+ Th2 cells into the airways in a mouse model of asthma.","volume":"179","author":"Jaffar","year":"2007","journal-title":"J. Immunol."},{"key":"2026012806273366000_r26","first-page":"81","article-title":"Effects of prostacyclin on aspecifically and specifically induced bronchoconstriction in asthmatic patients.","volume":"106","author":"Bianco","year":"1980","journal-title":"Eur. J. Respir. Dis. Suppl."},{"key":"2026012806273366000_r27","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1152\/jappl.1988.64.4.1567","article-title":"Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma.","volume":"64","author":"Hardy","year":"1988","journal-title":"J. Appl. Physiol."},{"key":"2026012806273366000_r28","doi-asserted-by":"crossref","first-page":"10303","DOI":"10.1128\/JVI.78.19.10303-10309.2004","article-title":"Signaling through the prostaglandin I2 receptor IP protects against respiratory syncytial virus-induced illness.","volume":"78","author":"Hashimoto","year":"2004","journal-title":"J. Virol."},{"key":"2026012806273366000_r29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1189\/jlb.70.2.185","article-title":"Insights into molecular mechanisms of contact hypersensitivity gained from gene knockout studies.","volume":"70","author":"Wang","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"2026012806273366000_r30","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1038\/jid.2008.5","article-title":"Cutaneous hypersensitivities to hapten are controlled by IFN-gamma-upregulated keratinocyte Th1 chemokines and IFN-gamma-downregulated langerhans cell Th2 chemokines.","volume":"128","author":"Mori","year":"2008","journal-title":"J. Invest. Dermatol."},{"key":"2026012806273366000_r31","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/41780","article-title":"Altered pain perception and inflammatory response in mice lacking prostacyclin receptor.","volume":"388","author":"Murata","year":"1997","journal-title":"Nature"},{"key":"2026012806273366000_r32","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.4049\/jimmunol.181.6.4311","article-title":"Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory response.","volume":"181","author":"Jessup","year":"2008","journal-title":"J. Immunol."},{"key":"2026012806273366000_r33","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.bbrc.2007.07.128","article-title":"CXCR4 engagement promotes dendritic cell survival and maturation.","volume":"361","author":"Kabashima","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026012806273366000_r34","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1172\/JCI15719","article-title":"src homology 2 domain-containing tyrosine phosphatase SHP-1 controls the development of allergic airway inflammation.","volume":"111","author":"Kamata","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2026012806273366000_r35","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/ni943","article-title":"Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity.","volume":"4","author":"Kabashima","year":"2003","journal-title":"Nat. Immunol."},{"key":"2026012806273366000_r36","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nm872","article-title":"Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells.","volume":"9","author":"Kabashima","year":"2003","journal-title":"Nat. Med."},{"key":"2026012806273366000_r37","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0167-5699(97)01186-9","article-title":"Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity.","volume":"19","author":"Grabbe","year":"1998","journal-title":"Immunol. Today"},{"key":"2026012806273366000_r38","doi-asserted-by":"crossref","first-page":"re4","DOI":"10.1126\/scisignal.122re4","article-title":"Pharmacological PKA inhibition: all may not be what it seems.","volume":"1","author":"Murray","year":"2008","journal-title":"Sci. Signal."},{"key":"2026012806273366000_r39","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1084\/jem.20051310","article-title":"Prostacyclin-IP signaling and prostaglandin E2-EP2\/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis.","volume":"203","author":"Honda","year":"2006","journal-title":"J. Exp. Med."},{"key":"2026012806273366000_r40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1600-065X.2008.00589.x","article-title":"T-cell activation through immunological synapses and kinapses.","volume":"221","author":"Dustin","year":"2008","journal-title":"Immunol. Rev."},{"key":"2026012806273366000_r41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2500\/108854186779045548","article-title":"Aspirin sensitive asthma and arachidonic acid transformation.","volume":"7","author":"Szczeklik","year":"1986","journal-title":"N. Engl. Reg. Allergy Proc."},{"key":"2026012806273366000_r42","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/sj.bjp.0704872","article-title":"Augmentation of allergic inflammation in prostanoid IP receptor deficient mice.","volume":"137","author":"Takahashi","year":"2002","journal-title":"Br. J. Pharmacol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/10\/5595\/62719198\/ji_0903260.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/10\/5595\/62719198\/ji_0903260.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:29:32Z","timestamp":1769599772000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/10\/5595\/8006793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2010,5,15]]},"published-print":{"date-parts":[[2010,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0903260","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,5]]},"published":{"date-parts":[[2010,5]]}}}