IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages

作者: Yayoi Sato , Hiromitsu Hara , Toshiaki Okuno , Naoko Ozaki , Shinobu Suzuki

DOI: 10.1016/J.BBRC.2014.07.096

关键词:

摘要: IL-27 is a heterodimeric cytokine that regulates both innate and adaptive immunity. The immunosuppressive effect of largely depends on induction IL-10-producing Tr1 cells. To date, however, effects regulation immune responses via mediators other than cytokines remain poorly understood. address this issue, we examined immunoregulatory conditional medium bone marrow-derived macrophages (BMDMs) from WSX-1 (IL-27Rα)-deficient mice found enhanced IFN-γ IL-17A secretion by CD4(+) T cells as compared with control BMDMs. We then PGE2 production COX-2 expression BMDMs WSX-1-deficient was increased to in response LPS. abolished EP2 EP4 antagonists, demonstrating responsible for production. Murine WSX-1-expressing Raw264.7 (mWSX-1-Raw264.7) showed phosphorylation STAT1 STAT3 produced less amounts parental RAW264.7 knockdown STAT1-deficiency higher their respective Collectively, our result indicated IL-27/WSX-1 regulated STAT1-COX-2 pathway affected helper cell PGE2-mediated fashion.

参考文章(20)
Alejandro V. Villarino, Elaine Huang, Christopher A. Hunter, Understanding the Pro- and Anti-Inflammatory Properties of IL-27 Journal of Immunology. ,vol. 173, pp. 715- 720 ,(2004) , 10.4049/JIMMUNOL.173.2.715
C. L. Zhu, Y. H. Cao, R. Zhang, Y. Song, W. Y. Liu, F. Pan, Y. Li, Y. Zhu, F. Liu, J. G. Wu, Stimulatory Effect of LPS and Feedback Effect of PGE2 on IL‐27 production Scandinavian Journal of Immunology. ,vol. 72, pp. 469- 475 ,(2010) , 10.1111/J.1365-3083.2010.02460.X
Hon-Wai Koon, Dezheng Zhao, Yanai Zhan, Sang Hoon Rhee, Mary P. Moyer, Charalabos Pothoulakis, Substance P Stimulates Cyclooxygenase-2 and Prostaglandin E2 Expression through JAK-STAT Activation in Human Colonic Epithelial Cells Journal of Immunology. ,vol. 176, pp. 5050- 5059 ,(2006) , 10.4049/JIMMUNOL.176.8.5050
Takeru Yoshimura, Atsunobu Takeda, Shinjiro Hamano, Yoshiyuki Miyazaki, Ichiko Kinjyo, Tatsuro Ishibashi, Akihiko Yoshimura, Hiroki Yoshida, Two-Sided Roles of IL-27: Induction of Th1 Differentiation on Naive CD4+ T Cells versus Suppression of Proinflammatory Cytokine Production Including IL-23-Induced IL-17 on Activated CD4+ T Cells Partially Through STAT3-Dependent Mechanism Journal of Immunology. ,vol. 177, pp. 5377- 5385 ,(2006) , 10.4049/JIMMUNOL.177.8.5377
Giorgio Trinchieri, Stefan Pflanz, Robert A Kastelein, The IL-12 Family of Heterodimeric Cytokines: New Players in the Regulation of T Cell Responses Immunity. ,vol. 19, pp. 641- 644 ,(2003) , 10.1016/S1074-7613(03)00296-6
Chengcan Yao, Daiji Sakata, Yoshiyasu Esaki, Youxian Li, Toshiyuki Matsuoka, Kenji Kuroiwa, Yukihiko Sugimoto, Shuh Narumiya, Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nature Medicine. ,vol. 15, pp. 633- 640 ,(2009) , 10.1038/NM.1968
J.S. Stumhofer, C.A. Hunter, Advances in understanding the anti-inflammatory properties of IL-27. Immunology Letters. ,vol. 117, pp. 123- 130 ,(2008) , 10.1016/J.IMLET.2008.01.011
Richard P. Phipps, Sidney H. Stein, Rachel L. Roper, A new view of prostaglandin E regulation of the immune response Immunology Today. ,vol. 12, pp. 349- 352 ,(1991) , 10.1016/0167-5699(91)90064-Z
Jason S Stumhofer, Arian Laurence, Emma H Wilson, Elaine Huang, Cristina M Tato, Leanne M Johnson, Alejandro V Villarino, Qiulong Huang, Akihiko Yoshimura, David Sehy, Christiaan J M Saris, John J O'Shea, Lothar Hennighausen, Matthias Ernst, Christopher A Hunter, Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nature Immunology. ,vol. 7, pp. 937- 945 ,(2006) , 10.1038/NI1376
Lei Xiao, Magdalena Ornatowska, Guiqing Zhao, Hongmei Cao, Rui Yu, Jing Deng, Yongchao Li, Qiong Zhao, Ruxana T. Sadikot, John W. Christman, Lipopolysaccharide-Induced Expression of Microsomal Prostaglandin E Synthase-1 Mediates Late-Phase PGE2 Production in Bone Marrow Derived Macrophages PLOS ONE. ,vol. 7, ,(2012) , 10.1371/JOURNAL.PONE.0050244