The anti-inflammatory mechanisms of Hsp70

Frontiers in Immunology

Volumn 3, Issue MAY, 2012, Pages

  Borges, Thiago J ^a   Wieten, Lotte ^b   Van Herwijnen, Martijn J C ^b   Broere, Femke ^b   Van derZee, Ruurd ^b   Bonorino, Cristina ^a   Van Eden, Willem ^b  

^a PONTIFICAL CATHOLIC UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^b UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Adaptive immunity; Hsp70; Immunomodulation; Innate immunity; Stress proteins

Indexed keywords

EID: 84865703584     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00095     Document Type: Review

References (136)

1. Aalberse, J. A., Kapitein, B., de Roock, S., Klein, M. R., de Jager, W., van der Zee, R., Hoekstra, M. O., van Wijk, E, and Prakken, B. J. (2011). Cord blood CD4 T cells respond to self heat shock protein 60 (HSP60). PLoS ONE 6, e24119. doi: 10.1371/journal. pone.0024119
2. Agrawal, A., Dillon, S., Denning, T. L., and Pulendran, B. (2006). ERK1-/- mice exhibit Th1 cell polarization and increased susceptibility to experimental autoimmune encephalomyelitis. J. Immunol. 176, 5788-5796.
3. Anderton, S. M., van der Zee, R., Prakken, B., Noordzij, A., and van Eden, W. (1995). Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis. J. Exp. Med. 181, 943-952.
4. Arispe, N., and De Maio, A. (2000). ATP and ADP modulate a cation channel formed by Hsc70 in acidic phospholipid membranes. J. Biol. Chem. 275, 30839-30843.
5. Arispe, N., Doh, M., Simakova, O., Kurganov,B.,and, DeMaio,A. (2004). Hsc70 and Hsp70 interact with phosphatidylserine on the surface of PC 12 cells resulting in a decrease of viability. FASEBJ. 18,1636-1645.
6. Asea, A., Kabingu, E., Stevenson, M. A., and Calderwood, S. K. (2000a). HSP70 peptidembearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones 5, 425-431.
7. Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W., Koo, G. C., and Calderwood, S. K. (2000b). HSP70 stimulates cytokine production through a CD 14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 6, 435-442.
8. Asea, A., Rehli, M., Kabingu, E., Boch, J. A., Bare, O., Auron, P. E., Stevenson, M. A., and Calderwood, S. K. (2002). Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277, 15028-15034.
9. Balog, A., Gyulai, Z., Boros, L. G., Farkas, G., Takacs, T., Lonovics, J., and Mandi, Y. (2005). Polymorphism of the TNF-alpha, HSP70-2, and CD 14 genes increases susceptibility to severe acute pancreatitis. Pancreas 30, e46-e50.
10. Barton, B. E. (2006). STAT3: a potential therapeutic target in dendritic cells for the induction of transplant tolerance. Expert Opin. Ther. Targets 10, 459-470.
11. Basu, S., Binder, R. J., Ramalingam, T., and Srivastava, P. K. (2001). CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14, 303-313.
12. Bausinger, H., Lipsker, D., Ziylan, U., Manie, S., Briand, J. P., Cazenave, J. P., Muller, S., Haeuw, J. F., Ravanat, C., de la Salle, H., and Hanau, D. (2002). Endotoxin-free heat-shock protein 70 fails to induce APC activation. Eur. I Immunol. 32, 3708-3713.
13. Bellmann, K., Hui, L., Radons, J., Burkart,V.,andKolb, H. (1997). Low stress response enhances vulnerability of islet cells in diabetes-prone BB rats. Diabetes 46, 232-236.
14. Binder, R. J. (2009). CD40-independent engagement of mammalian hsp70 by antigen-presenting cells. J. Immunol. 182,6844-6850.
15. Blass, S., Union, A., Raymackers, J., Schumann, F., Ungethum, U., Muller-Steinbach, S., de Keyser, F., Engel, J. M., and Burmester, G. R. (2001). The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis. Arthritis Rheum. 44,761-771.
16. Bluestone, J. A. (2005). Regulatory T cell therapy: is it ready for the clinic? Nat. Rev. Immunol. 5, 343-349.
17. Bogunia-Kubik, K., and Lange, A. (2005). HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease. Transplantation 79, 815-820.
18. Bonorino, C., Nardi, N. B., Zhang, X., and Wysocki, L. J. (1998). Characteristics of the strong antibody response to mycobacterial Hsp70: a primary, T cell-dependent IgG response with no evidence of natural priming or gamma delta T cell involvement. J. Immunol. 161,5210-5216.
19. Boog, C. J., de Graeff-Meeder, E. R., Lucassen, M. A., van der Zee, R., Voorhorst-Ogink, M. M., van Kooten, P. J., Geuze, H. J., and van Eden, W. (1992). Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J. Exp. Med. 175, 1805-1810.
20. Borges, T. J., Porto, B. N., Teixeira, C. A., Rodrigues, M., Machado, E D., Ornaghi, A. P., de Souza, A. P., Maito, F., Pavanelli, W. R., Silva, J. S., and Bonorino, C. (2010). Prolonged survival of allografts induced by mycobacterial Hsp70 is dependent on CD4+CD25+ regulatory T cells. PLoS ONE 5, e14264. doi: 10.1371/journal.pone.0014264
21. Botzler, C., Li, G., Issels, R. D., and Multhoff, G. (1998). Definition of extracellular localized epitopes of Hsp70 involved in an NK immune response. Cell Stress Chaperones 3, 6-11.
22. Broere, F., van der Zee, R., and van Eden, W. (2011). Heat shock proteins are no DAMPs, rather 'DAMPERs'. Nat. Rev. Immunol. 11, 565; author reply 565.
23. Brusko, T. M., Putnam, A. L., and Blue-stone, J.A. (2008). Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol. Rev. 223, 371-390.
24. Burkart, V., Germaschewski, L.,Schloot, N. C., Bellmann, K., and Kolb, H. (2008). Deficient heat shock protein 70 response to stress in leukocytes at onset of type 1 diabetes. Biochem. Biophys. Res. Commun. 369, 421-425.
25. Bussolati, B., Rollino, C., Mariano, F., Quarello, F., and Camussi, G. (2000). IL-10 stimulates production of platelet-activating factor by monocytes of patients with active systemic lupus erythematosus (SLE). Clin. Exp. Immunol. 122, 471-476.
26. Chalmin, F., Ladoire, S., Mignot, G., Vincent, J., Bruchard, M., Remy-Martin, J. P., Boireau, W., Rouleau, A., Simon, B., Lanneau, D., de Thonel, A., Multhoff, G., Ham-man, A., Martin, F., Chauffert, B., Solary, E., Zitvogel, L., Garrido, C., Ryffel, B., Borg, C., Apetoh, L., Rebe, C., and Ghiringhelli, E (2010). Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppres-sive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest. 120,457-471.
27. Chen, Y., Kuchroo, V. K., Inobe, J., Hafler, D. A., and Weiner, H. L. (1994). Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237-1240.
28. Clarimon, J., Bertranpetit, J., Boada, M., Tarraga, L., and Comas, D. (2003). HSP70-2 (HSPA1B) is associated with noncognitive symptoms in late-onset Alzheimer's disease. J. Geriatr. Psychiatry Neurol. 16, 146-150.
29. Cohen, I. R. (2007). Biomarkers, self-antigens and the immunologi-cal homunculus. J. Autoimmun. 29, 246-249.
30. Cohen, I. R., and Young, D. B. (1991). Autoimmunity, microbial immunity and the immunological homunculus. Immunol. Today 12, 105-110.
31. Debler, J., Schiemann, U., Seybold, U., Mussack, T., Landauer, N., Ladurner, R., and Gross, M. (2003). Heat-shock protein HSP70-2 genotypes in patients with Crohn's disease: a more severe clinical course with intestinal complications in presence of the PstI-polymorphism. Eur. J. Med. Res. 8, 120-124.
32. de Graeff-Meeder, E. R., van der Zee, R., Rijkers, G. T., Schuurman, H. J., Kuis, W., Bijlsma, J. W., Zegers, B. J., and van Eden, W. (1991). Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis. Lancet 337, 1368-1372.
33. de Graeff-Meeder, E. R., van Eden, W., Rijkers, G. T., Prakken, B. J., Kuis, W., Voorhorst-Ogink, M. M., van der Zee, R., Schuurman, H. J., Helders, P. J., and Zegers, B. J. (1995). Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. J. Clin. Invest. 95, 934-940.
34. de Kleer, I. M., Kamphuis, S. M., Rijkers, G. T., Scholtens, L., Gordon, G., de Jager, W., Hafner, R., van de Zee, R., van Eden, W., Kuis, W., and Prakken, B. J. (2003). The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat-shock protein 60 capable of producing the regulatory cytokine interleukin-10. Arthritis Rheum. 48, 2001-2010.
35. Delneste, Y., Magistrelli, G., Gauchat, J., Haeuw, J., Aubry, J., Nakamura, K., Kawakami-Honda, N., Goetsch, L., Sawamura, T., Bonnefoy, J., and Jean-nin, P. (2002). Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17, 353-362.
36. De Maio, A. (2011). Extracellular heat shock proteins, cellular export vesicles, and the Stress Observation System: a form of communication during injury, infection, and cell damage. It is never known how far a controversial finding will go! Dedicated to Fer-ruccio Ritossa. Cell Stress Chaperones 16,235-249.
37. Dengjel, J., Schoor, O., Fischer, R., Reich, M., Kraus, M., Muller, M., Kreym-borg, K., Altenberend, F., Brandenburg, J., Kalbacher, H., Brock, R., Driessen, C., Rammensee, H. G., and Stevanovic, S. (2005). Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc. Natl. Acad. Sci. U.S.A. 102,7922-7927.
38. Detanico, T., Rodrigues, L., Sabritto, A. C., Keisermann, M., Bauer, M. E., Zwickey, H., and Bonorino, C. (2004). Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation. Clin. Exp. Immunol. 135, 336-342.
39. Dhingra, S., Bagchi, A. K., Ludke, A. L., Sharma, A. K., and Singal, P. K. (2011). Akt regulates IL-10 mediated suppression of TNFα-induced cardiomyocyte apoptosis by upreg-ulating Stat3 phosphorylation. PLoS ONE 6, e25009. doi: 10.1371/journal. pone.0025009
40. Dillon, S., Agrawal, A., van Dyke, T., Landreth, G., Mccauley, L., Koh, A., Maliszewski, C., Akira, S., and Pulen-dran, B. (2004). A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signal-regulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells. J. Immunol. 172, 4733-4743.
41. Dillon, S., Agrawal, S., Banerjee, K., Letterio, J., Denning, T. L., Oswald-Richter, K., Kasprowicz, D. J., Kellar, K., Pare, J., van Dyke, T., Ziegler, S., Unutmaz, D., and Pulendran, B. (2006). Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J. Clin. Invest. 116,916-928.
42. Dong, C., Davis, R. J., and Flavell, R. A. (2002). MAP kinases in the immune response. Annu. Rev. Immunol. 20, 55-72.
43. Ellis, R. J. (1990). The molecular chap-erone concept. Semin. Cell Biol. 1, 1-9.
44. Feder, M. E., and Hofmann, G. E. (1999). Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu. Rev. Physiol. 61, 243-282.
45. Ferrarini, M., Heltai, S., Zocchi, M. R., and Rugarli, C. (1992). Unusual expression and localization of heat-shock proteins in human tumor cells. Int. I Cancer 51, 613-619.
46. Feuerer, M., Hill, J. A., Mathis, D., and Benoist, C. (2009). Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat. Immunol. 10, 689-695.
47. Fischer, H. P., Sharrock, C. E., and Panayi, G. S. (1992). High frequency of cord blood lymphocytes against mycobacterial 65-kDa heat-shock protein. Eur. J. Immunol. 22, 1667-1669.
48. Floto, R. A., Macary, P. A., Boname, J. M., Mien, T. S., Kampmann, B., Hair, J. R., Huey, O. S., Houben, E. N., Pieters, J., Day, C., Oehlmann, W., Singh, M., Smith, K. G., and Lehner, P. J. (2006). Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5. Science 314, 454-458.
49. Frodermann, V., Chau, T. A., Sayedya-hossein, S., Toth, J. M., Heinrichs, D. E., and Madrenas, J. (2011). A modulatory interleukin-10 response to staphylococcal peptidoglycan prevents Th1/Th17 adaptive immunity to Staphylococcus aureus. J. Infect. Dis. 204,253-262.
50. Gabrilovich, D. I., and Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162-174.
51. Gao, B. C., and Tsan, M. F. (2004). Induction of cytokines by heat shock proteins and endotoxin in murine macrophages. Biochem. Biophys. Res. Commun. 317, 1149-1154.
52. Gehrmann, M., Radons, J., Molls, M., and Multhoff, G. (2008). The therapeutic implications of clinically applied modifiers of heat shock protein 70 (Hsp70) expression by tumor cells. Cell Stress Chaperones 13, 1-10.
53. Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., de Vries, J. E., and Roncarolo, M. G. (1997). A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742.
54. Halfter, H., Friedrich, M., Postert, C., Ringelstein, E. B., and Stogbauer, F. (1999). Activation of Jak-Stat and MAPK2 pathways by oncostatin M leads to growth inhibition of human glioma cells. Mol Cell Biol. Res. Commun. 1,109-116.
55. Heath, W. R., and Carbone, F. R. (2009). Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nat. Immunol. 10, 1237-1244.
56. Hightower, L. E., and Guidon, P. T. Jr. (1989). Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins.J. Cell. Physiol. 138,257-266.
57. Horwitz, D. A., Zheng, S. G., and Gray, J. D. (2008). Natural and TGF-beta-induced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other. Trends Immunol. 29, 429-435.
58. Janson, A. A., Klatser, P. R., van der Zee, R., Cornelisse, Y. E., de Vries, R. R., Thole, J. E., and Ottenhoff, T. H. (1991). A systematic molecular analysis of the T cell-stimulating antigens from Mycobacterium leprae with T cell clones of leprosy patients. Identification of a novel M. leprae HSP 70 fragment by M. leprae-specific T cells. J. Immunol. 147, 3530-3537.
59. Jenkins, M. K., Chen, C. A., Jung, G., Mueller, D. L., and Schwartz, R. H. (1990). Inhibition of antigen-specific proliferation of type 1 murine T cell clones after stimulation with immobilized anti-CD3 monoclonal antibody.J. Immunol. 144, 16-22.
60. Kaiser, F., Cook, D., Papoutsopoulou, S., Rajsbaum, R., Wu, X., Yang, H. T., Grant, S., Ricciardi-Castagnoli, P., Tsichlis, P. N., Ley, S. C., and O'Garra, A. (2009). TPL-2 negatively regulates interferon-beta production in macrophages and myeloid dendritic cells. J. Exp. Med. 206, 1863-1871.
61. Kammerer, R., Stober, D., Riedl, P., Oehninger, C., Schirmbeck, R., and Reimann, J. (2002). Noncovalent association with stress protein facilitates cross-priming of CD8+ T cells to tumor cell antigens by dendritic cells. J. Immunol. 168,108-117.
62. Kampinga, H. H., Hageman, J., Vos, M. J., Kubota, H., Tanguay, R. M., Bruford, E. A., Cheetham, M. E., Chen, B., and Hightower, L. E. (2009). Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14, 105-111.
63. Kaufmann, S. H., Vath, U., Thole, J. E., van Embden, J. D., and Emm-rich, F. (1987). Enumeration of T cells reactive with Mycobacterium tuberculosis organisms and specific for the recombinant mycobacterial 64-kDa protein. Eur. J. Immunol. 17, 351-357.
64. Kimura, Y., Yamada, K., Sakai, T., Mishima, K., Nishimura, H., Mat-sumoto, Y., Singh, M., and Yoshikai, Y (1998). The regulatory role of heat shock protein 70-reactive CD4+ T cells during rat listeriosis. Int. Immunol. 10,117-130.
65. Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshi-mori, T., Ohsumi, Y., Tokuhisa, T., and Mizushima, N. (2004). The role of autophagy during the early neonatal starvation period. Nature 432, 1032-1036.
66. Li, D., Romain, G., Flamar, A. L., Duluc, D., Dullaers, M., Li, X. H., Zurawski, S., Bosquet, N., Palucka, A. K., Le Grand, R., O'Garra, A., Zurawski, G., Banchereau, J., and Oh, S. (2012). Targeting self- and foreign antigens to dendritic cells viaDC-ASGPRgenerates IL-10-producing suppressive CD4+ T cells. J. Exp. Med. 209, 109-121.
67. Lindquist, S. (1986). The heat-shock response. Annu. Rev. Biochem. 55, 1151-1191.
68. Lindquist, S., and Craig, E. A. (1988). The heat-shock proteins. Annu. Rev. Genet. 22, 631-677.
69. Long, S. A., Rieck, M., Tatum, M., Bol-lyky, P. L., Wu, R. P., Muller, I., Ho, J. C., Shilling, H. G., and Buckner, J. H. (2011). Low-dose antigen promotes induction of FOXP3 in human CD4+ T cells. J. Immunol. 187, 3511-3520.
70. Luo,X.,Zuo,X., Zhou, Y.,Zhang,B., Shi, Y., Liu, M., Wang, K., Mcmillian, D. R., and Xiao, X. (2008). Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proin-flammatory mediator production in fibroblast-like synoviocytes. Arthritis Res. Ther. 10,R41.
71. Manicassamy, S., Ravindran, R., Deng, J., Oluoch, H., Denning, T. L., Kas-turi, S. P., Rosenthal, K. M., Evavold, B. D., and Pulendran, B. (2009). Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoim-munity. Nat. Med. 15,401-409.
72. Mekala, D. J., Alli, R. S., and Geiger, T. L. (2005). IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T lymphocytes. Proc. Natl. Acad. Sci. USA 102, 11817-11822.
73. Moore, K. W., de Waal Malefyt, R., Coff-man, R. L., and O'Garra, A. (2001). Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683-765.
74. Morelli, A. E., and Thomson, A. W. (2007). Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7, 610-621.
75. Motta, A., Schmitz, C., Rodrigues, L., Ribeiro, F., Teixeira, C., Detan-ico, T., Bonan, C., Zwickey, H., and Bonorino, C. (2007). Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro. Immunology 121,462-472.
76. Multhoff, G., Botzler, C., Wiesnet, M., Muller, E., Meier, T., Wilmanns, W., and Issels, R. D. (1995). A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int. J. Cancer 61, 272-279.
77. Munk, M. E., Schoel, B., Modrow, S., Karr, R. W., Young, R. A., and Kaufmann, S. H. (1989). T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein. J. Immunol. 143, 2844-2849.
78. Munz, C. (2006). Autophagy and antigen presentation. Cell. Microbiol. 8, 891-898.
79. Munz, C. (2009). Enhancing immunity through autophagy. Annu. Rev. Immunol. 27, 423-449.
80. Murray, P. J. (2006). Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response. Curr. Opin. Pharmacol. 6, 379-386.
81. Murray, P. J. (2007). The JAK-STAT signaling pathway: input and output integration. J. Immunol. 178, 2623-2629.
82. Neefjes, J., Jongsma, M. L., Paul, P., and Bakke, O. (2011). Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol. 11, 823-836.
83. Njemini, R., Lambert, M., Demanet, C., Vanden Abeele, M., Vandebosch, S., and Mets, T. (2003). The induction of heat shock protein 70 in peripheral mononuclear blood cells in elderly patients: a role for inflammatory markers. Hum. Immunol. 64, 575-585.
84. Peluso, I., Fantini, M. C., Fina, D., Caruso, R., Boirivant, M., Macdon-ald, T. T., Pallone, F., and Monteleone, G. (2007). IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J. Immunol. 178,732-739.
85. Pockley, A. G., Shepherd, J., and Cor-ton, J. M. (1998). Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol. Invest. 27, 367-377.
86. Prakken, B. J., Wendling, U., van der Zee, R., Rutten, V. P., Kuis, W., and van Eden, W. (2001). Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins. J. Immunol. 167,4147-4153.
87. Qin, S., Cobbold, S. P., Pope, H., Elliott, J., Kioussis, D., Davies, J., and Waldmann, H. (1993). "Infectious" transplantation tolerance. Science 259, 974-977.
88. Quayle, A. J., Wilson, K. B., Li, S. G., Kjeldsen-Kragh, J., Oftung, F., Shinnick, T., Sioud, M., Forre, O., Capra, J. D., and Natvig, J. B. (1992). Peptide recognition, T cell receptor usage and HLA restriction elements of human heat-shock protein (hsp) 60 and mycobacterial 65-kDa hsp-reactive T cell clones from rheumatoid synovial fluid. Eur. J. Immunol. 22,1315-1322.
89. Rao, D. V., Watson, K., and Jones, G. L. (1999). Age-related attenuation in the expression of the major heat shock proteins in human peripheral lymphocytes. Mech. Ageing Dev. 107, 105-118.
90. Roncarolo, M. G., and Battaglia, M. (2007). Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat. Rev. Immunol. 7, 585-598.
91. Rosenblum, M. D., Gratz, I. K., Paw, J. S., Lee, K., Marshak-Rothstein, A., and Abbas, A. K. (2011). Response to self antigen imprints regulatory memory in tissues. Nature 480, 538-542.
92. Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W R. Jr., Muller, W., and Rudensky, A. Y. (2008). Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28, 546-558.
93. Rutella, S., Danese, S., and Leone, G. (2006). Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108, 1435-1440.
94. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164.
95. Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. (2008). Regulatory T cells and immune tolerance. Cell 133, 775-787.
96. Saraiva, M., and O'Garra, A. (2010). The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 10,170-181.
97. Schett, G., Redlich, K., Xu, Q., Bizan, P., Groger, M., Tohidast-Akrad, M., Kiener, H., Smolen, J., and Steiner, G. (1998). Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue. Differential regulation of hsp70 expression and hsf 1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and antiin-flammatory drugs. J. Clin. Invest. 102, 302-311.
98. Schick, C., Arbogast, M., Lowka, K., Rzepka, R., and Melchers, I. (2004). Continuous enhanced expression of Hsc70 but not Hsp70 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 50, 88-93.
99. Schmid, D., and Munz, C. (2007). Immune surveillance via self digestion. Autophagy 3, 133-135.
100. Schmid, D., Pypaert, M., and Munz, C. (2007). Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophago-somes. Immunity 26, 79-92.
101. Sela, U., Olds, P., Park, A., Schlesinger, S. J., and Steinman, R. M. (2011). Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice. J. Exp. Med. 208, 2489-2496.
102. Sharif, M. N., Tassiulas, I., Hu, Y., Mecklenbrauker, I., Tarakhovsky, A., and Ivashkiv, L. B. (2004). IFN-alpha priming results in a gain of proinflammatory function by IL-10: implications for systemic lupus erythematosus pathogenesis. J. Immunol. 172,6476-6481.
103. Shevach, E. M. (2006). From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 25, 195-201.
104. Steinman, R. M., Hawiger, D., and Nussenzweig, M. C. (2003). Tolerogenic dendritic cells. Annu. Rev. Immunol. 21,685-711.
105. Steinman, R. M., Turley, S., Mellman, I., and Inaba, K. (2000). The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191,411-416.
106. Stocki, P., Wang, X. N., and Dickinson, A. M. (2012). Inducible Hsp70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells. J. Biol. Chem. 287, 12387-12394.
107. Stokes, C. R., Haverson, K., and Bailey, M. (1996). Antigen presenting cells in the porcine gut. Vet. Immunol. Immunopathol. 54, 171-177.
108. Stordeur, P., and Goldman, M. (1998).Interleukin-10asaregulatory cytokine induced by cellular stress: molecular aspects. Int. Rev. Immunol. 16,501-522.
109. Strawbridge, A. B., and Blum, J. S. (2007). Autophagy in MHC class II antigen processing. Curr. Opin. Immunol. 19,87-92.
110. Tanaka, K., Namba, T., Arai, Y., Fujimoto, M., Adachi, H., Sobue, G., Takeuchi, K., Nakai, A., and Mizushima, T. (2007). Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis. J. Biol. Chem. 282, 23240-23252.
111. Tanaka, S., Kimura, Y., Mitani, A., Yamamoto, G., Nishimura, H., Spallek, R., Singh, M., Noguchi, T., and Yoshikai, Y (1999). Activation of T cells recognizing an epitope of heat-shock protein 70 can protect against rat adjuvant arthritis. J. Immunol. 163,5560-5565.
112. Tang, Q., and Bluestone, J. A. (2008). The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat. Immunol. 9, 239-244.
113. Tarbell, K. V., Petit, L., Zuo, X., Toy, P., Luo, X., Mqadmi, A., Yang, H., Suthanthiran, M., Mojsov, S., and Steinman, R. M. (2007). Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J. Exp. Med. 204, 191-201.
114. Theriault, J. R., Adachi, H., and Calder-wood, S.K. (2006). Role of scavenger receptors in the binding and internal-ization of heat shock protein 70. J. Immunol. 177,8604-8611.
115. Theriault, J. R., Mambula, S. S., Sawa-mura, T., Stevenson, M. A., and Calderwood, S. K. (2005). Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells. FEBSLett. 579, 1951-1960.
116. Thornton, A. M., Korty, P. E., Tran, D.Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., and Shevach, E. M. (2010). Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells.J. Immunol. 184, 3433-3441.
117. Tsan, M. F., and Gao, B. (2009). Heat shock proteins and immune system. J.Leukoc. Biol. 85,905-910.
118. Udono, H., and Srivastava, P. K. (1993). Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med. 178, 1391-1396.
119. Ueda, G., Tamura, Y., Hirai, I., Kamiguchi, K., Ichimiya, S., Tori-goe, T., Hiratsuka, H., Sunakawa, H., and Sato, N. (2004). Tumor-derived heat shock protein 70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity. Cancer Sci. 95, 248-253.
120. Valencia, X., Stephens, G., Goldbach-Mansky, R., Wilson, M., Shevach, E.M., and Lipsky, P. E. (2006). TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood 108, 253-261.
121. van Eden, W., Thole, J. E., van der Zee, R., Noordzij, A., van Embden, J. D., Hensen, E. J., and Cohen, I. R. (1988). Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331,171-173.
122. van Eden, W., van der Zee, R., and Prakken, B. (2005). Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat. Rev. Immunol. 5,318-330.
123. van Eden, W., Wick, G., Albani, S., and Cohen, I. (2007). Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases. Ann. NY Acad. Sci. 1113, 217-237.
124. van Puijvelde, G. H., van Es, T., van Wanrooij, E. J., Habets, K. L., de Vos, P., van der Zee, R., van Eden, W., van Berkel, T. J., and Kuiper, J. (2007). Induction of oral tolerance to HSP60 or an HSP60-peptide activates T cell regulation and reduces atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 27, 2677-2683.
125. Vega, V. L., Rodriguez-Silva, M., Frey, T., Gehrmann, M., Diaz, J. C., Steinem, C., Multhoff, G., Arispe, N., and de Maio, A. (2008). Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J. Immunol. 180, 4299-4307.
126. Vignali, D. A., Collison, L. W., and Workman, C. J. (2008). How regulatory T cells work. Nat. Rev. Immunol. 8, 523-532.
127. Wang, Y., Kelly, C. G., Karttunen, J. T., Whittall, T., Lehner, P. J., Duncan, L., Macary, P., Younson, J. S., Singh, M., Oehlmann, W., Cheng, G., Bergmeier, L., and Lehner, T. (2001). CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 15,971-983.
128. Watowich, S. S., and Liu, Y. J. (2010). Mechanisms regulating dendritic cell specification and development. Immunol. Rev. 238, 76-92.
129. Wauben, M. H., van der Zee, R., Joosten, I., Boog, C. J., van Dijk, A. M., Holewijn, M. C., Meloen, R. H., and van Eden, W. (1993). A peptide variant of an arthritis-related T cell epitope induces T cells that recognize this epitope as a synthetic peptide but not in its naturally processed form. J. Immunol. 150, 5722-5730.
130. Weiner, H. L. (2001). Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol. Rev. 182, 207-214.
131. Wendling, U., Paul, L., van der Zee, R., Prakken, B., Singh, M., and van Eden, W. (2000). A conserved mycobacterial heat shock protein (hsp) 70 sequence prevents adjuvant arthritis upon nasal administration and induces IL-10-producing T cells that cross-react with the mammalian self-hsp70 homologue. J. Immunol. 164, 2711-2717.
132. Wieten, L., Berlo, S. E., Ten Brink, C. B., van Kooten, P. J., Singh, M., van der Zee, R., Glant, T. T., Broere, E, and van Eden, W. (2009a). IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis. PLoS ONE 4, e4186. doi: 10.1371/journal. pone.0004186
133. Wieten, L., van der Zee, R., Goedemans, R., Sijtsma, J., Serafini, M., Lubsen, N. H., van Eden, W., and Broere, E. (2009b). Hsp70 expression and induction as a readout for detection of immune modulatory components in food. Cell Stress Chaperones 15, 25-37.
134. Wieten, L., van der Zee, R., Spiering, R., Wagenaar-Hilbers, J., van Kooten, P., Broere, F., and van Eden, W. (2010). A novel heat-shock protein coinducer boosts stress protein Hsp70 to activate T cell regulation of inflammation in autoimmune arthritis. Arthritis Rheum. 62, 1026-1035.
135. Yamazaki, S., Okada, K., Maruyama, A., Matsumoto, M., Yagita, H., and Seya, T. (2011). TLR2-dependent induction of IL-10 and Foxp3+ CD25+ CD4+ regulatory T cells prevents effective anti-tumor immunity induced by Pam2 lipopeptides in vivo. PLoS ONE 6, e18833. doi: 10.1371/journal.pone.0018833
136. Yi, A. K., Yoon, J. G., Yeo, S. J., Hong, S. C., English, B. K., and Krieg, A. M. (2002). Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response. J. Immunol. 168,4711-4720.