Peptidylarginine deiminase inhibition impairs toll-like receptor agonist-induced functional maturation of dendritic cells, resulting in the loss of T cell–proliferative capacity: A partial mechanism with therapeutic potential in inflammatory settings

Journal of Leukocyte Biology

Volumn 97, Issue 2, 2015, Pages 351-362

  Jang, Byungki ^a   Kim, Ho Won ^a   Kim, Jong Seok ^a   Kim, Woo Sik ^a   Lee, Bo Ryeong ^b   Kim, Sojeong ^a   Kim, Hongmin ^a   Han, Seung Jung ^a   Ha, Sang Jun ^b   Shin, Sung Jae ^a  

^a Yonsei University College of Medicine   (South Korea)

^b Yonsei University   (South Korea)

Author keywords

Citrullination; Cl amidine; Cytokine

Indexed keywords

ANTIGEN; B7 ANTIGEN; CL AMIDINE; ENZYME INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 12P70; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN ARGININE DEIMINASE; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG; CYTOKINE; HYDROLASE; N-ALPHA-BENZOYL-N5-(2-CHLORO-1-IMINOETHYL)-L-ORNITHINE AMIDE; ORNITHINE; PROTEIN-ARGININE DEIMINASE; TOLL LIKE RECEPTOR;

ANIMAL CELL; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL MATURATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITE; DENDRITIC CELL; DOWN REGULATION; ENZYME INHIBITION; FEMALE; IMMUNOCOMPETENT CELL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INFLAMMATORY DISEASE; INTRACELLULAR SPACE; MOUSE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE; TRANSMISSION ELECTRON MICROSCOPY; AGONISTS; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; DRUG EFFECTS; IMMUNOLOGY; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ANTIGENS, CD80; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; CYTOKINES; DENDRITIC CELLS; FEMALE; HYDROLASES; INFLAMMATION; LIPOPOLYSACCHARIDES; MAP KINASE SIGNALING SYSTEM; MICE; NF-KAPPA B; ORNITHINE; TOLL-LIKE RECEPTORS;

EID: 84925371234     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.3A0314-142RR     Document Type: Article

References (46)

1. Vossenaar, E. R., Zendman, A. J. W., van Venrooij, W. J., Pruijn, G. J. M. (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. BioEssays 25, 1106–1118.
2. Foulquier, C., Sebbag, M., Clavel, C., Chapuy-Regaud, S., Al Badine, R., Méchin, M. C., Vincent, C., Nachat, R., Yamada, M., Takahara, H., Simon, M., Guerrin, M., Serre, G. (2007) Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. 56, 3541–3553.
3. Li, P., Yao, H., Zhang, Z., Li, M., Luo, Y., Thompson, P. R., Gilmour, D. S., Wang, Y. (2008) Regulation of p53 target gene expression by peptidylarginine deiminase 4. Mol. Cell. Biol. 28, 4745–4758.
4. Zhang, X., Bolt, M., Guertin, M. J., Chen, W., Zhang, S., Cherrington, B. D., Slade, D. J., Dreyton, C. J., Subramanian, V., Bicker, K. L., Thompson, P. R., Mancini, M. A., Lis, J. T., Coonrod, S. A. (2012) Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor a target gene activation. Proc. Natl. Acad. Sci. USA 109, 13331–13336.
5. Cuthbert, G. L., Daujat, S., Snowden, A. W., Erdjument-Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P. D., Tempst, P., Bannister, A. J., Kouzarides, T. (2004) Histone deimination antagonizes arginine methylation. Cell 118, 545–553.
6. Slack, J. L., Causey, C. P., Thompson, P. R. (2011) Protein arginine deiminase 4: a target for an epigenetic cancer therapy. Cell. Mol. Life Sci. 68, 709–720.
7. Wang, Y., Li, M., Stadler, S., Correll, S., Li, P., Wang, D., Hayama, R., Leonelli, L., Han, H., Grigoryev, S. A., Allis, C. D., Coonrod, S. A. (2009) Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J. Cell Biol. 184, 205–213.
8. Li, P., Li, M., Lindberg, M. R., Kennett, M. J., Xiong, N., Wang, Y. (2010) PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J. Exp. Med. 207, 1853–1862.
9. Moelants, E. A. V., Mortier, A., Van Damme, J., Proost, P., Loos, T. (2012) Peptidylarginine deiminases: physiological function, interaction with chemokines and role in pathology. Drug Discov. Today. Technol. 9, e227–e314.
10. Moelants, E. A. V., Mortier, A., Grauwen, K., Ronsse, I., Van Damme, J., Proost, P. (2013) Citrullination of TNF-a by peptidylarginine deiminases reduces its capacity to stimulate the production of inflammatory chemokines. Cytokine 61, 161–167.
11. Jang, B., Shin, S. J. (2013) Peptidylarginine deiminase and citrullination: potential therapeutic targets for inflammatory diseases. J. Bacteriol. Virol. 43, 159–167.
12. Willis, V. C., Gizinski, A. M., Banda, N. K., Causey, C. P., Knuckley, B., Cordova, K. N., Luo, Y., Levitt, B., Glogowska, M., Chandra, P., Kulik, L., Robinson, W. H., Arend, W. P., Thompson, P. R., Holers, V. M. (2011) Nalpha- Benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collageninduced arthritis. J. Immunol. 186, 4396–4404.
13. Chumanevich, A. A., Causey, C. P., Knuckley, B. A., Jones, J. E., Poudyal, D., Chumanevich, A. P., Davis, T, Matesic, L. E., Thompson, P. R., Hofseth, L. J. (2011) Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor. Am. J. Physiol. Gastrointest Liver Physiol. 300, G929–G938.
14. Knight, J. S., Zhao, W., Luo, W., Subramanian, V., O’Dell, A. A., Yalavarthi, S., Hodgin, J. B., Eitzman, D. T., Thompson, P. R., Kaplan, M. J. (2013) Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus. J. Clin. Invest. 123, 2981–2993.
15. Knight, J. S., Luo, W., O’Dell, A. A., Yalavarthi, S., Zhao, W., Subramanian, V., Guo, C., Grenn, R. C., Thompson, P. R., Eitzman, D. T., Kaplan, M. J. (2014) Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ. Res. 114, 947–956.
16. Moscarello, M. A., Lei, H., Mastronardi, F. G., Winer, S., Tsui, H., Li, Z., Ackerley, C., Zhang, L., Raijmakers, R., Wood, D. D. (2013) Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis. Dis. Model. Mech. 6, 467–478.
17. Wang, Y., Li, P., Wang, S., Hu, J., Chen, X. A., Wu, J., Fisher, M., Oshaben, K., Zhao, N., Gu, Y., Wang, D., Chen, G., Wang, Y. (2012) Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activity. J. Biol. Chem. 287, 25941–25953.
18. Ganguly, D., Haak, S., Sisirak, V., Reizis, B. (2013) The role of dendritic cells in autoimmunity. Nat. Rev. Immunol. 13, 566–577.
19. Steinman, R. M. (2006) Linking innate to adaptive immunity through dendritic cells. Novartis Found. Symp. 279, 101-109; discussion 109-113, 216-219.
20. Khan, S., Greenberg, J. D., Bhardwaj, N. (2009) Dendritic cells as targets for therapy in rheumatoid arthritis. Nat. Rev. Rheumatol. 5, 566–571.
21. Blanco, P., Palucka, A. K., Pascual, V., Banchereau, J. (2008) Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 19, 41–52.
22. Jang, B., Jin, J. K., Jeon, Y. C., Cho, H. J., Ishigami, A., Choi, K. C., Carp, R. I., Maruyama, N., Kim, Y. S., Choi, E. K. (2010) Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease. Acta Neuropathol. 119, 199–210.
23. Vander Lugt, B., Khan, A. A., Hackney, J. A., Agrawal, S., Lesch, J., Zhou, M., Lee, W. P., Park, S., Xu, M., DeVoss, J., Spooner, C. J., Chalouni, C., Delamarre, L., Mellman, I., Singh, H. (2014) Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation. Nat. Immunol. 15, 161–167.
24. Quah, B. J., Warren, H. S., Parish, C. R. (2007) Monitoring lymphocyte proliferation in vitro and in vivo with the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester. Nat. Protoc. 2, 2049–2056.
25. Egan, R. M., Yorkey, C., Black, R., Loh, W. K., Stevens, J. L., Storozynsky, E., Lord, E. M., Frelinger, J. G., Woodward, J. G. (2000) In vivo behavior of peptide-specific T cells during mucosal tolerance induction: antigen introduced through the mucosa of the conjunctiva elicits prolonged antigenspecific T cell priming followed by anergy. J. Immunol. 164, 4543–4550.
26. Walton, K. L., Galanko, J. A., Balfour Sartor, R., Fisher, N. C. (2006) T Cell-mediated oral tolerance is intact in germ-free mice. Clin. Exp. Immunol. 143, 503–512.
27. Luckashenak, N., Schroeder, S., Endt, K., Schmidt, D., Mahnke, K., Bachmann, M. F., Marconi, P., Deeg, C. A., Brocker, T. (2008) Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivo. Immunity 28, 521–532.
28. Zhang, G., Ghosh, S. (2001) Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J. Clin. Invest. 107, 13–19.
29. Luo, Y., Arita, K., Bhatia, M., Knuckley, B., Lee, Y. H., Stallcup, M. R., Sato, M., Thompson, P. R. (2006) Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. Biochemistry 45, 11727–11736.
30. Shumilina, E., Huber, S.M., Lang, F. (2011) Ca2+ signaling in the regulation of dendritic cell functions. Am. J. Physiol. Cell Physiol. 300, C1205–C1214.
31. Ireland, J., Herzog, J., Unanue, E. R. (2006) Cutting edge: unique T cells that recognize citrullinated peptides are a feature of protein immunization. J. Immunol. 177, 1421–1425.
32. Ireland, J. M., Unanue, E. R. (2011) Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells. J. Exp. Med. 208, 2625–2632.
33. Feitsma, A. L., van der Voort, E. I., Franken, K. L., el Bannoudi, H., Elferink, B. G., Drijfhout, J. W., Huizinga, T. W., de Vries, R. R., Toes, R. E., Ioan-Facsinay, A. (2010) Identification of citrullinated vimentin peptides as T cell epitopes in HLA-DR4-positive patients with rheumatoid arthritis. Arthritis Rheum. 62, 117–125.
34. Law, S. C., Street, S., Yu, C. H., Capini, C., Ramnoruth, S., Nel, H. J., van Gorp, E., Hyde, C., Lau, K., Pahau, H., Purcell, A. W., Thomas, R. (2012) T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles. Arthritis Res. Ther. 14, R118.
35. Pritzker, L. B., Joshi, S., Gowan, J. J., Harauz, G., Moscarello, M. A. (2000) Deimination of myelin basic protein. 1. Effect of deimination of arginyl residues of myelin basic protein on its structure and susceptibility to digestion by cathepsin D. Biochemistry 39, 5374–5381.
36. Kudo, O., Sabokbar, A., Pocock, A., Itonaga, I., Fujikawa, Y., Athanasou, N. A. (2003) Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism. Bone 32, 1–7.
37. Huang, Y. M., Xiao, B. G., Ozenci, V., Kouwenhoven, M., Teleshova, N., Fredrikson, S., Link, H. (1999) Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines. J. Neuroimmunol. 99, 82–90.
38. Karni, A., Abraham, M., Monsonego, A., Cai, G., Freeman, G. J., Hafler, D., Khoury, S. J., Weiner, H. L. (2006) Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response. J. Immunol. 177, 4196–4202.
39. Mannon, P. J., Fuss, I J.,Mayer, L., Elson, C. O., Sandborn, W. J., Present, D., Dolin B.,Goodman, N.,Groden, C.,Hornung, R. L.,Quezado, M., Yang, Z., Neurath, M. F., Salfeld, J., Veldman, G. M., Schwertschlag, U., Strober, W.; Anti-IL-12 Crohn’s Disease Study Group. (2004) Anti-interleukin-12 antibody for active Crohn’s disease. N. Engl. J. Med. 351, 2069–2079.
40. Neurath, M. F., Fuss, I., Kelsall, B. L., Stüber, E., Strober, W. (1995) Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 182, 1281–1290.
41. Ludewig, B., Junt, T., Hengartner, H., Zinkernagel, R. M. (2001) Dendritic cells in autoimmune diseases. Curr. Opin. Immunol. 13, 657–662.
42. Eriksson, U., Ricci, R., Hunziker, L., Kurrer, M. O., Oudit, G. Y., Watts, T. H., Sonderegger, I., Bachmaier, K., Kopf, M., Penninger, J. M. (2003) Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat. Med. 9, 1484–1490.
43. Pagni, P. P., Traub, S., Demaria, O., Chasson, L., Alexopoulou, L. (2010) Contribution of TLR7 and TLR9 signaling to the susceptibility of MyD88- deficient mice to myocarditis. Autoimmunity 43, 275–287.
44. McMahon, E. J., Bailey, S. L., Castenada, C. V., Waldner, H., Miller, S. D. (2005) Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med. 11, 335–339.
45. Greter, M., Heppner, F. L., Lemos, M. P., Odermatt, B. M., Goebels, N., Laufer, T., Noelle, R. J., Becher, B. (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat. Med. 11, 328–334.
46. O’Neill, S. K., Shlomchik, M. J., Glant, T. T., Cao, Y., Doodes, P. D., Finnegan, A. (2005) Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J. Immunol. 174, 3781–3788.