On the role of the immunoproteasome in transplant rejection

  • Michael Basler
  • Jun Li
  • Marcus Groettrup
Part of the following topical collections:
  1. Biology and Evolution of Antigen Presentation


The immunoproteasome is expressed in cells of hematopoietic origin and is induced during inflammation by IFN-γ. Targeting the immunoproteasome with selective inhibitors has been shown to be therapeutically effective in pre-clinical models for autoimmune diseases, colitis-associated cancer formation, and transplantation. Immunoproteasome inhibition prevents activation and proliferation of lymphocytes, lowers MHC class I cell surface expression, reduces the expression of cytokines of activated immune cells, and curtails  T helper 1 and 17 cell differentiation. This might explain the in vivo efficacy of immunoproteasome inhibition in different pre-clinical disease models for autoimmunity, cancer, and transplantation. In this review, we summarize the effect of immunoproteasome inhibition in different animal models for transplantation.


Proteasome Immunoproteasome Antigen processing Antigen presentation Transplantation 


Funding information

This work was funded by the German Research Foundation grant Nr. BA 4199/2-1 to M.B. and GR 1517/2.4, GR 1517/10-2, and SFB969 (project C01) to M.G. as well as by the Else Kröner-Fresenius-Stiftung grant 2017_A28 to M.G., and by the National Natural Science Foundation of China (81870304) and China Scholarship Council (201508500057) to J.L.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Adams J, Behnke M, Chen SW, Cruickshank AA, Dick LR, Grenier L, Klunder JM, Ma YT, Plamondon L, Stein RL (1998) Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg Med Chem Lett 8:333–338CrossRefGoogle Scholar
  2. Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ (1999) Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 59:2615–2622PubMedGoogle Scholar
  3. Alexander T, Sarfert R, Klotsche J, Kuhl AA, Rubbert-Roth A, Lorenz HM, Rech J, Hoyer BF, Cheng Q, Waka A, Taddeo A, Wiesener M, Schett G, Burmester GR, Radbruch A, Hiepe F, Voll RE (2015) The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus. Ann Rheum Dis 74:1474–1478CrossRefGoogle Scholar
  4. Al-Homsi AS, Cole K, Bogema M, Duffner U, Williams S, Mageed A (2015) Short course of post-transplantation cyclophosphamide and bortezomib for graft-versus-host disease prevention after allogeneic peripheral blood stem cell transplantation is feasible and yields favorable results: a phase I study. Biol Blood Marrow Transplant 21:1315–1320CrossRefGoogle Scholar
  5. Al-Homsi AS, Cole K, Muilenburg M, Goodyke A, Abidi M, Duffner U, Williams S, Parker J, Abdel-Mageed A (2017) Calcineurin and mTOR inhibitor-free post-transplantation cyclophosphamide and bortezomib combination for graft-versus-host disease prevention after peripheral blood allogeneic hematopoietic stem cell transplantation: a phase I/II study. Biol Blood Marrow Transplant 23:1651–1657CrossRefGoogle Scholar
  6. Althof N, Goetzke CC, Kespohl M, Voss K, Heuser A, Pinkert S, Kaya Z, Klingel K, Beling A (2018) The immunoproteasome-specific inhibitor ONX 0914 reverses susceptibility to acute viral myocarditis. EMBO Mol Med 10:200–218CrossRefGoogle Scholar
  7. Arpinati M, Chirumbolo G, Nicolini B, Agostinelli C, Rondelli D (2009) Selective apoptosis of monocytes and monocyte-derived DCs induced by bortezomib (Velcade). Bone Marrow Transplant 43:253–259CrossRefGoogle Scholar
  8. Basler M, Beck U, Kirk CJ, Groettrup M (2011) The antiviral immune response in mice devoid of immunoproteasome activity. J Immunol 187:5548–5557CrossRefGoogle Scholar
  9. Basler M, Dajee M, Moll C, Groettrup M, Kirk CJ (2010) Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. J Immunol 185:634–641CrossRefGoogle Scholar
  10. Basler M, Kirk CJ, Groettrup M (2013) The immunoproteasome in antigen processing and other immunological functions. Curr Opin Immunol 25:74–80CrossRefGoogle Scholar
  11. Basler M, Lauer C, Beck U, Groettrup M (2009) The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. J Immunol 183:6145–6150CrossRefGoogle Scholar
  12. Basler M, Maurits E, de Bruin G, Koerner J, Overkleeft HS, Groettrup M (2018) Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome. Br J Pharmacol 175:38–52CrossRefGoogle Scholar
  13. Basler M, Moebius J, Elenich L, Groettrup M, Monaco JJ (2006) An altered T cell repertoire in MECL-1-deficient mice. J Immunol 176:6665–6672CrossRefGoogle Scholar
  14. Basler M, Mundt S, Groettrup M (2018) The immunoproteasome subunit LMP7 is required in the murine thymus for filling up a hole in the T cell repertoire. Eur J Immunol 48:419–429CrossRefGoogle Scholar
  15. Basler M, Mundt S, Muchamuel T, Moll C, Jiang J, Groettrup M, Kirk CJ (2014) Inhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis. EMBO Mol Med 6:226–238PubMedPubMedCentralGoogle Scholar
  16. Basler M, Youhnovski N, Van Den Broek M, Przybylski M, Groettrup M (2004) Immunoproteasomes down-regulate presentation of a subdominant T cell epitope from lymphocytic choriomeningitis virus. J Immunol 173:3925–3934CrossRefGoogle Scholar
  17. Berges C, Haberstock H, Fuchs D, Miltz M, Sadeghi M, Opelz G, Daniel V, Naujokat C (2008) Proteasome inhibition suppresses essential immune functions of human CD4+ T cells. Immunology 124:234–246CrossRefGoogle Scholar
  18. Blanco B, Perez-Simon JA, Sanchez-Abarca LI, Carvajal-Vergara X, Mateos J, Vidriales B, Lopez-Holgado N, Maiso P, Alberca M, Villaron E, Schenkein D, Pandiella A, San Miguel J (2006) Bortezomib induces selective depletion of alloreactive T lymphocytes and decreases the production of Th1 cytokines. Blood 107:3575–3583CrossRefGoogle Scholar
  19. Chen S, Kammerl IE, Vosyka O, Baumann T, Yu Y, Wu Y, Irmler M, Overkleeft HS, Beckers J, Eickelberg O, Meiners S, Stoeger T (2016) Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages. Cell Death Differ 23:1026–1037CrossRefGoogle Scholar
  20. Chen WS, Norbury CC, Cho YJ, Yewdell JW, Bennink JR (2001) Immunoproteasomes shape immunodominance hierarchies of antiviral CD8(+) T cells at the levels of T cell repertoire and presentation of viral antigens. J Exp Med 193:1319–1326CrossRefGoogle Scholar
  21. Chen X, Zhang X, Chen T, Jiang X, Wang X, Lei H, Wang Y (2018) Inhibition of immunoproteasome promotes angiogenesis via enhancing hypoxia-inducible factor-1alpha abundance in rats following focal cerebral ischaemia. Brain Behav Immun 73:167–179CrossRefGoogle Scholar
  22. Chou B, Hisaeda H, Shen J, Duan X, Imai T, Tu L, Murata S, Tanaka K, Himeno K (2008) Critical contribution of immunoproteasomes in the induction of protective immunity against Trypanosoma cruzi in mice vaccinated with a plasmid encoding a CTL epitope fused to green fluorescence protein. Microbes Infect 10:241–250CrossRefGoogle Scholar
  23. Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I (2016) Proteasome or immunoproteasome inhibitors cause apoptosis in human renal tubular epithelial cells under normoxic and hypoxic conditions. Int Urol Nephrol 48:907–915CrossRefGoogle Scholar
  24. Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I (2017) A comparative analysis between proteasome and immunoproteasome inhibition in cellular and humoral alloimmunity. Int Immunopharmacol 50:48–54CrossRefGoogle Scholar
  25. Ersching J, Vasconcelos JR, Ferreira CP, Caetano BC, Machado AV, Bruna-Romero O, Baron MA, Ferreira LR, Cunha-Neto E, Rock KL, Gazzinelli RT, Rodrigues MM (2016) The combined deficiency of immunoproteasome subunits affects both the magnitude and quality of pathogen- and genetic vaccination-induced CD8+ T cell responses to the human protozoan parasite Trypanosoma cruzi. PLoS Pathog 12:e1005593CrossRefGoogle Scholar
  26. Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, Hidalgo LG, Haslacher H, Kaltenecker CC, Aretin MB, Oberbauer R, Posch M, Staudenherz A, Handisurya A, Reeve J, Halloran PF, Bohmig GA (2018) A randomized trial of bortezomib in late antibody-mediated kidney transplant rejection. J Am Soc Nephrol 29:591–605CrossRefGoogle Scholar
  27. Everly MJ, Everly JJ, Susskind B, Brailey P, Arend LJ, Alloway RR, Roy-Chaudhury P, Govil A, Mogilishetty G, Rike AH, Cardi M, Wadih G, Tevar A, Woodle ES (2008) Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantation 86:1754–1761CrossRefGoogle Scholar
  28. Farini A, Sitzia C, Cassani B, Cassinelli L, Rigoni R, Colleoni F, Fusco N, Gatti S, Bella P, Villa C, Napolitano F, Maiavacca R, Bosari S, Villa A, Torrente Y (2016) Therapeutic potential of immunoproteasome inhibition in Duchenne muscular dystrophy. Mol Ther 24:1898–1912CrossRefGoogle Scholar
  29. Fehling HJ, Swat W, Laplace C, Kuehn R, Rajewsky K, Mueller U, von Boehmer H (1994) MHC class I expression in mice lacking proteasome subunit LMP-7. Science 265:1234–1237CrossRefGoogle Scholar
  30. Gorbacheva V, Fan R, Li X, Valujskikh A (2010) Interleukin-17 promotes early allograft inflammation. Am J Pathol 177:1265–1273CrossRefGoogle Scholar
  31. Groettrup M, Kirk CJ, Basler M (2010) Proteasomes in immune cells: more than peptide producers? Nat Rev Immunol 10:73–78CrossRefGoogle Scholar
  32. Guimaraes G, Gomes MTR, Campos PC, Marinho FV, de Assis NRG, Silveira TN, Oliveira SC (2018) Immunoproteasome subunits are required for CD8(+) T cell function and host resistance to Brucella abortus infection in mice. Infect Immun 20;86(3):e00615–17Google Scholar
  33. Guo Y, Chen X, Li D, Liu H, Ding Y, Han R, Shi Y, Ma X (2018) PR-957 mediates neuroprotection by inhibiting Th17 differentiation and modulating cytokine production in a mouse model of ischaemic stroke. Clin Exp Immunol 193(2):194–206.CrossRefGoogle Scholar
  34. Hartono C, Muthukumar T, Suthanthiran M (2013) Immunosuppressive drug therapy. Cold Spring Harb Perspect Med 3:a015487CrossRefGoogle Scholar
  35. Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M (2012) Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell 148:727–738CrossRefGoogle Scholar
  36. Hutchinson S, Sims S, O'Hara G, Silk J, Gileadi U, Cerundolo V, Klenerman P (2011) A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PLoS One 6:e14646CrossRefGoogle Scholar
  37. Ichikawa HT, Conley T, Muchamuel T, Jiang J, Lee S, Owen T, Barnard J, Nevarez S, Goldman BI, Kirk CJ, Looney RJ, Anolik JH (2012) Novel proteasome inhibitors have a beneficial effect in murine lupus via the dual inhibition of type I interferon and autoantibody secreting cells. Arthritis Rheum 64:493–503CrossRefGoogle Scholar
  38. Ikeda T, Fujii H, Nose M, Kamogawa Y, Shirai T, Shirota Y, Ishii T, Harigae H (2017) Bortezomib treatment induces a higher mortality rate in lupus model mice with a higher disease activity. Arthritis Res Ther 19:187CrossRefGoogle Scholar
  39. Ingulli E (2010) Mechanism of cellular rejection in transplantation. Pediatr Nephrol 25:61–74CrossRefGoogle Scholar
  40. Itoh S, Kimura N, Axtell RC, Velotta JB, Gong Y, Wang X, Kajiwara N, Nambu A, Shimura E, Adachi H, Iwakura Y, Saito H, Okumura K, Sudo K, Steinman L, Robbins RC, Nakae S, Fischbein MP (2011) Interleukin-17 accelerates allograft rejection by suppressing regulatory T cell expansion. Circulation 124:S187–S196CrossRefGoogle Scholar
  41. Jiang S, Herrera O, Lechler RI (2004) New spectrum of allorecognition pathways: implications for graft rejection and transplantation tolerance. Curr Opin Immunol 16:550–557CrossRefGoogle Scholar
  42. Van Kaer L, Ashton-Rickardt PG, Eichelberger M, Gaczynska M, Nagashima K, Rock KL, Goldberg AL, Doherty PC, Tonegawa S (1994) Altered peptidase and viral-specific T cell response in LMP 2 mutant mice. Immunity 1:533–541CrossRefGoogle Scholar
  43. Kalim KW, Basler M, Kirk CJ, Groettrup M (2012) Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation. J Immunol 189:4182–4193CrossRefGoogle Scholar
  44. Kincaid EZ, Che JW, York I, Escobar H, Reyes-Vargas E, Delgado JC, Welsh RM, Karow ML, Murphy AJ, Valenzuela DM, Yancopoulos GD, Rock KL (2012) Mice completely lacking immunoproteasomes show major changes in antigen presentation. Nat Immunol 13:129–135CrossRefGoogle Scholar
  45. Kincaid EZ, Murata S, Tanaka K, Rock KL (2016) Specialized proteasome subunits have an essential role in the thymic selection of CD8(+) T cells. Nat Immunol 17:938–945CrossRefGoogle Scholar
  46. Koerner J, Brunner T, Groettrup M (2017) Inhibition and deficiency of the immunoproteasome subunit LMP7 suppress the development and progression of colorectal carcinoma in mice. Oncotarget 8:50873–50888CrossRefGoogle Scholar
  47. Koreth J, Kim HT, Lange PB, Bindra B, Reynolds CG, Chammas MJ, Armand P, Cutler CS, Ho VT, Glotzbecker B, Nikiforow S, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP 3rd (2015) A bortezomib-based regimen offers promising survival and graft-versus-host disease prophylaxis in myeloablative HLA-mismatched and unrelated donor transplantation: a phase II trial. Biol Blood Marrow Transplant 21:1907–1913CrossRefGoogle Scholar
  48. Koreth J, Kim HT, Lange PB, Poryanda SJ, Reynolds CG, Rai SC, Armand P, Cutler CS, Ho VT, Glotzbecker B, Yusuf R, Nikiforow S, Chen YB, Dey B, McMasters M, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP 3rd (2018) Bortezomib-based immunosuppression after reduced-intensity conditioning hematopoietic stem cell transplantation: randomized phase II results. Haematologica 103:522–530CrossRefGoogle Scholar
  49. Koreth J, Stevenson KE, Kim HT, McDonough SM, Bindra B, Armand P, Ho VT, Cutler C, Blazar BR, Antin JH, Soiffer RJ, Ritz J, Alyea EP 3rd (2012) Bortezomib-based graft-versus-host disease prophylaxis in HLA-mismatched unrelated donor transplantation. J Clin Oncol 30:3202–3208CrossRefGoogle Scholar
  50. Kremer M, Henn A, Kolb C, Basler M, Moebius J, Guillaume B, Leist M, Van den Eynde BJ, Groettrup M (2010) Reduced immunoproteasome formation and accumulation of immunoproteasomal precursors in the brains of lymphocytic choriomeningitis virus-infected mice. J Immunol 185:5549–5560CrossRefGoogle Scholar
  51. Li J, Basler M, Alvarez G, Brunner T, Kirk CJ, Groettrup M (2018) Immunoproteasome inhibition prevents chronic antibody-mediated allograft rejection in renal transplantation. Kidney Int 93:670–680CrossRefGoogle Scholar
  52. Liu W, Ren HY, Dong YJ, Wang LH, Yin Y, Li Y, Qiu ZX, Cen XN, Shi YJ (2012) Bortezomib regulates the chemotactic characteristics of T cells through downregulation of CXCR3/CXCL9 expression and induction of apoptosis. Int J Hematol 96:764–772CrossRefGoogle Scholar
  53. Liu H, Wan C, Ding Y, Han R, He Y, Xiao J, Hao J (2017) PR-957, a selective inhibitor of immunoproteasome subunit low-MW polypeptide 7, attenuates experimental autoimmune neuritis by suppressing Th17 cell differentiation and regulating cytokine production. FASEB J 31(4):1756-1766.CrossRefGoogle Scholar
  54. Liu RT, Zhang P, Yang CL, Pang Y, Zhang M, Zhang N, Yue LT, Li XL, Li H, Duan RS (2017) ONX-0914, a selective inhibitor of immunoproteasome, ameliorates experimental autoimmune myasthenia gravis by modulating humoral response. J Neuroimmunol 311:71–78CrossRefGoogle Scholar
  55. Mishto M, Liepe J, Textoris-Taube K, Keller C, Henklein P, Weberruss M, Dahlmann B, Enenkel C, Voigt A, Kuckelkorn U, Stumpf MP, Kloetzel PM (2014) Proteasome isoforms exhibit only quantitative differences in cleavage and epitope generation. Eur J Immunol 44:3508–3521CrossRefGoogle Scholar
  56. Muchamuel T, Basler M, Aujay MA, Suzuki E, Kalim KW, Lauer C, Sylvain C, Ring ER, Shields J, Jiang J, Shwonek P, Parlati F, Demo SD, Bennett MK, Kirk CJ, Groettrup M (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15:781–787CrossRefGoogle Scholar
  57. Mundt S, Basler M, Buerger S, Engler H, Groettrup M (2016) Inhibiting the immunoproteasome exacerbates the pathogenesis of systemic Candida albicans infection in mice. Sci Rep 6:19434CrossRefGoogle Scholar
  58. Mundt S, Basler M, Sawitzki B, Groettrup M (2017) No prolongation of skin allograft survival by immunoproteasome inhibition in mice. Mol Immunol 88:32–37CrossRefGoogle Scholar
  59. Mundt S, Engelhardt B, Kirk CJ, Groettrup M, Basler M (2016) Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMV-induced meningitis. Eur J Immunol 46:104–113CrossRefGoogle Scholar
  60. Nagayama Y, Nakahara M, Shimamura M, Horie I, Arima K, Abiru N (2012) Prophylactic and therapeutic efficacies of a selective inhibitor of the immunoproteasome for Hashimoto’s thyroiditis, but not for Graves’ hyperthyroidism, in mice. Clin Exp Immunol 168:268–273CrossRefGoogle Scholar
  61. Nencioni A, Garuti A, Schwarzenberg K, Cirmena G, Dal Bello G, Rocco I, Barbieri E, Brossart P, Patrone F, Ballestrero A (2006) Proteasome inhibitor-induced apoptosis in human monocyte-derived dendritic cells. Eur J Immunol 36:681–689CrossRefGoogle Scholar
  62. Neubert K, Meister S, Moser K, Weisel F, Maseda D, Amann K, Wiethe C, Winkler TH, Kalden JR, Manz RA, Voll RE (2008) The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med 14:748–755CrossRefGoogle Scholar
  63. Osterloh P, Linkemann K, Tenzer S, Rammensee HG, Radsak MP, Busch DH, Schild H (2006) Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses. Proc Natl Acad Sci U S A 103:5042–5047CrossRefGoogle Scholar
  64. Pearl MH, Nayak AB, Ettenger RB, Puliyanda D, Palma Diaz MF, Zhang Q, Reed EF, Tsai EW (2016) Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection. Pediatr Nephrol 31:1341–1348CrossRefGoogle Scholar
  65. Rock KL, Gramm C, Rothstein L, Clark K, Stein R, Dick L, Hwang D, Goldberg AL (1994) Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761–771CrossRefGoogle Scholar
  66. Santos RLA, Bai L, Singh PK, Murakami N, Fan H, Zhan W, Zhu Y, Jiang X, Zhang K, Assker JP, Nathan CF, Li H, Azzi J, Lin G (2017) Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes. Nat Commun 8:1692CrossRefGoogle Scholar
  67. Saric T, Beninga J, Graef CI, Akopian TN, Rock KL, Goldberg AL (2001) Major histocompatibility complex class I-presented antigenic peptides are degraded in cytosolic extracts primarily by thimet oligopeptidase. J Biol Chem 276:36474–36481CrossRefGoogle Scholar
  68. Shrikant P, Khoruts A, Mescher MF (1999) CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity 11:483–493CrossRefGoogle Scholar
  69. Straube C, Wehner R, Wendisch M, Bornhauser M, Bachmann M, Rieber EP, Schmitz M (2007) Bortezomib significantly impairs the immunostimulatory capacity of human myeloid blood dendritic cells. Leukemia 21:1464–1471CrossRefGoogle Scholar
  70. Sula Karreci E, Fan H, Uehara M, Mihali AB, Singh PK, Kurdi AT, Solhjou Z, Riella LV, Ghobrial I, Laragione T, Routray S, Assaker JP, Wang R, Sukenick G, Shi L, Barrat FJ, Nathan CF, Lin G, Azzi J (2016) Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice. Proc Natl Acad Sci U S A 113:E8425–E8432CrossRefGoogle Scholar
  71. Sun K, Welniak LA, Panoskaltsis-Mortari A, O'Shaughnessy MJ, Liu H, Barao I, Riordan W, Sitcheran R, Wysocki C, Serody JS, Blazar BR, Sayers TJ, Murphy WJ (2004) Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Proc Natl Acad Sci U S A 101:8120–8125CrossRefGoogle Scholar
  72. Toes REM, Nussbaum AK, Degermann S, Schirle M, Emmerich NPN, Kraft M, Laplace C, Zwinderman A, Dick TP, Muller J, Schonfisch B, Schmid C, Fehling HJ, Stevanovic S, Rammensee HG, Schild H (2001) Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products. J Exp Med 194:1–12CrossRefGoogle Scholar
  73. Treise I, Huber EM, Klein-Rodewald T, Heinemeyer W, Grassmann SA, Basler M, Adler T, Rathkolb B, Helming L, Andres C, Klaften M, Landbrecht C, Wieland T, Strom TM, McCoy KD, Macpherson AJ, Wolf E, Groettrup M, Ollert M, Neff F, Gailus-Durner V, Fuchs H, Hrabe de Angelis M, Groll M, Busch DH (2018) Defective immuno- and thymoproteasome assembly causes severe immunodeficiency. Sci Rep 8:5975CrossRefGoogle Scholar
  74. Trivedi HL, Terasaki PI, Feroz A, Everly MJ, Vanikar AV, Shankar V, Trivedi VB, Kaneku H, Idica AK, Modi PR, Khemchandani SI, Dave SD (2009) Abrogation of anti-HLA antibodies via proteasome inhibition. Transplantation 87:1555–1561CrossRefGoogle Scholar
  75. Vachharajani N, Joeris T, Luu M, Hartmann S, Pautz S, Jenike E, Pantazis G, Prinz I, Hofer MJ, Steinhoff U, Visekruna A (2017) Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7. Oncotarget 8:50447–50459CrossRefGoogle Scholar
  76. Vogelbacher R, Meister S, Guckel E, Starke C, Wittmann S, Stief A, Voll R, Daniel C, Hugo C (2010) Bortezomib and sirolimus inhibit the chronic active antibody-mediated rejection in experimental renal transplantation in the rat. Nephrol Dial Transplant 25:3764–3773CrossRefGoogle Scholar
  77. Walsh RC, Everly JJ, Brailey P, Rike AH, Arend LJ, Mogilishetty G, Govil A, Roy-Chaudhury P, Alloway RR, Woodle ES (2010) Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection. Transplantation 89:277–284CrossRefGoogle Scholar
  78. Xiao F, Lin X, Tian J, Wang X, Chen Q, Rui K, Ma J, Wang S, Wang Q, Wang X, Liu D, Sun L, Lu L (2017) Proteasome inhibition suppresses Th17 cell generation and ameliorates autoimmune development in experimental Sjogren’s syndrome. Cell Mol ImmunolGoogle Scholar
  79. Zilberberg J, Matos J, Dziopa E, Dziopa L, Yang Z, Kirk CJ, Assefnia S, Korngold R (2015) Inhibition of the immunoproteasome subunit LMP7 with ONX 0914 ameliorates graft-versus-host disease in an MHC-matched minor histocompatibility antigen-disparate murine model. Biol Blood Marrow Transplant 21:1555–1564CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Immunology, Department of BiologyUniversity of KonstanzKonstanzGermany
  2. 2.Biotechnology Institute Thurgau (BITg)University of KonstanzKreuzlingenSwitzerland
  3. 3.Department of Urology Oncological SurgeryChongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer HospitalChongqingChina

Personalised recommendations