The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo

Blood

Volumn 122, Issue 7, 2013, Pages 1192-1202

  Heine, Annkristin ^a   Held, Stefanie Andrea Erika ^a   Daecke, Solveig Nora ^a   Wallner, Stephanie ^b   Yajnanarayana, Sowmya Parampalli ^a   Kurts, Christian ^c   Wolf, Dominik ^a   Brossart, Peter ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b UNIVERSITY HOSPITAL INNSBRUCK   (Austria)

^c UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

B7 ANTIGEN; CD40 ANTIGEN; CD69 ANTIGEN; CD83 ANTIGEN; CD86 ANTIGEN; GLYCOPROTEIN P 15095; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HLA DR ANTIGEN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 12; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 4; LIPOPOLYSACCHARIDE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; OVALBUMIN; RUXOLITINIB; T6 ANTIGEN; CYTOKINE; JANUS KINASE; PYRAZOLE DERIVATIVE;

ADENOVIRUS INFECTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOLUMINESCENCE; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL DIFFERENTIATION; CELL MATURATION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOTOXICITY; DENDRITIC CELL; DOWN REGULATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MIXED LYMPHOCYTE REACTION; MONOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION; UPREGULATION; VIRAL CLEARANCE; VIRUS LOAD; ANIMAL; ANTIGEN PRESENTING CELL; APOPTOSIS; BONE MARROW; C57BL MOUSE; CELL ADHESION; CELL CULTURE; CELL MOTION; CYTOLOGY; CYTOTOXIC T LYMPHOCYTE; DRUG ANTAGONISM; DRUG EFFECT; FLOW CYTOMETRY; IMMUNOLOGY; METABOLISM; SPLEEN; TRANSGENIC MOUSE; WESTERN BLOTTING;

ANIMALS; ANTIGEN-PRESENTING CELLS; APOPTOSIS; BLOTTING, WESTERN; BONE MARROW; CELL ADHESION; CELL DIFFERENTIATION; CELL MOVEMENT; CELL PROLIFERATION; CELLS, CULTURED; CYTOKINES; DENDRITIC CELLS; FLOW CYTOMETRY; HUMANS; JANUS KINASES; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MONOCYTES; PYRAZOLES; SPLEEN; T-LYMPHOCYTES, CYTOTOXIC;

EID: 84887193830     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2013-03-484642     Document Type: Article

References (36)

1. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med. 2000;342(17):1255-1265.
2. Percy MJ, McMullin MF. The V617F JAK2 mutation and the myeloproliferative disorders. Hematol Oncol. 2005;23(3-4):91-93.
3. Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007;7(9):673-683.
4. Quintás-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010;115(15):3109-3117.
5. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012; 366(9):787-798.
6. Santos FP, Verstovsek S. JAK2 inhibitors for myelofibrosis: why are they effective in patients with and without JAK2V617F mutation? Anticancer Agents Med Chem. 2012;12(9): 1098-1109.
7. Kurts C, Robinson BW, Knolle PA. Cross-priming in health and disease. Nat Rev Immunol. 2010; 10(6):403-414.
8. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767-811.
9. Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem. 2007;282(28):20059-20063.
10. Zhong J, Yang P, Muta K, et al. Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock. PLoS ONE. 2010;5(3):e9593.
11. Conzelmann M, Wagner AH, Hildebrandt A, et al. IFN-g activated JAK1 shifts CD40-induced cytokine profiles in human antigen-presenting cells toward high IL-12p70 and low IL-10 production. Biochem Pharmacol. 2010;80(12): 2074-2086.
12. Grünebach F, Erndt S, Häntschel M, Heine A, Brossart P. Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells. Cancer Immunol Immunother. 2008;57(10):1483-1491.
13. Kock G, Bringmann A, Held SA, Daecke S, Heine A, Brossart P. Regulation of dectin-1-mediated dendritic cell activation by peroxisome proliferator-activated receptor-gamma ligand troglitazone. Blood. 2011;117(13):3569-3574.
14. Inaba K, Inaba M, Romani N, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/ macrophage colony-stimulating factor. J Exp Med. 1992;176(6):1693-1702.
15. Lutz MB, Kukutsch N, Ogilvie AL, et al. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 1999; 223(1):77-92.
16. Semmling V, Lukacs-Kornek V, Thaiss CA, et al. Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs. Nat Immunol. 2010;11(4):313-320.
17. Appel S, Mirakaj V, Bringmann A, Weck MM, Grünebach F, Brossart P. PPAR-gamma agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-kappaB pathways. Blood. 2005;106(12):3888-3894.
18. Bringmann A, Schmidt SM, Weck MM, et al. Zoledronic acid inhibits the function of Toll-like receptor 4 ligand activated monocyte-derived dendritic cells. Leukemia. 2007;21(4):732-738.
19. von Schwarzenberg K, Held SA, Schaub A, Brauer KM, Bringmann A, Brossart P. Proteasome inhibition overcomes the resistance of renal cell carcinoma cells against the PPARgamma ligand troglitazone. Cell Mol Life Sci. 2009;66(7):1295-1308.
20. Held SA, Duchardt KM, Tenzer S, et al. Imatinib mesylate and nilotinib affect MHC-class I presentation by modulating the proteasomal processing of antigenic peptides. Cancer Immunol Immunother. 2013;62(4):715-726.
21. Hardy S, Kitamura M, Harris-Stansil T, Dai Y, Phipps ML. Construction of adenovirus vectors through Cre-lox recombination. J Virol. 1997; 71(3):1842-1849.
22. Sprinzl MF, Oberwinkler H, Schaller H, Protzer U. Transfer of hepatitis B virus genome by adenovirus vectors into cultured cells and mice: crossing the species barrier. J Virol. 2001;75(11): 5108-5118.
23. Stabenow D, Frings M, Trück C, et al. Bioluminescence imaging allows measuring CD8 T cell function in the liver. Hepatology. 2010; 51(4):1430-1437.
24. Chan VW, Kothakota S, Rohan MC, et al. Secondary lymphoid-tissue chemokine (SLC) is chemotactic for mature dendritic cells. Blood. 1999;93(11):3610-3616.
25. Fleischmann R, Kremer J, Cush J, et al; ORAL Solo Investigators. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495-507.
26. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994;179(4):1109-1118.
27. Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228(1):273-287.
28. Jahrsdörfer B, Vollmer A, Blackwell SE, et al. Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion. Blood. 2010;115(6):1156-1165.
29. Rivas-Caicedo A, Soldevila G, Fortoul TI, Castell-Rodríguez A, Flores-Romo L, García-Zepeda EA. Jak3 is involved in dendritic cell maturation and CCR7-dependent migration. PLoS ONE. 2009; 4(9):e7066.
30. Yarilina A, Xu K, Chan C, Ivashkiv LB. Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 2012;64(12):3856-3866.
31. Rosengren S, Corr M, Firestein GS, Boyle DL. The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type I interferon. Ann Rheum Dis. 2012;71(3): 440-447.
32. Tsai YT, Chen YH, Chang DM, Chen PC, Lai JH. Janus kinase/signal transducer and activator of transcription 3 signaling pathway is crucial in chemokine production from hepatocytes infected by dengue virus. Exp Biol Med (Maywood). 2011; 236(10):1156-1165.
33. Wysham NG, Sullivan DR, Allada G. An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor. Chest. 2013; 143(5):1478-1479.
34. Kwatra SG, Dabade TS, Gustafson CJ, Feldman SR. JAK inhibitors in psoriasis: a promising new treatment modality. J Drugs Dermatol. 2012; 11(8):913-918.
35. Punwani N, Scherle P, Flores R, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol. 2012;67(4):658-664.
36. Fridman JS, Scherle PA, Collins R, et al. Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. J Invest Dermatol. 2011;131(9):1838-1844.