REVIEW PAPER
Heat shock proteins (HSPs) in the homeostasis of regulatory T cells (Tregs)
Submission date: 2015-07-20
Final revision date: 2015-12-07
Acceptance date: 2015-12-14
Publication date: 2016-10-25
Cent Eur J Immunol 2016;41(3):317-323
KEYWORDS
ABSTRACT
Heat shock proteins (HSPs) belong to the family of conservative polypeptides with a high homology of the primary structure. The uniqueness of this family lies in their ability to interact with a large number of different proteins and provide protection from cellular and environmental stress factors as molecular chaperones to keep protein homeostasis. While intracellular HSPs play a mainly protective role, extracellular or membrane-bound HSPs mediate immunological functions and immunomodulatory activity. In immune system are subsets of cells including regulatory T cells (Tregs) with suppressive functions. HSPs are implicated in the function of innate and adaptive immune systems, stimulate T lymphocyte proliferation and immunomodulatory functions, increase the effectiveness of cross-presentation of antigens, and induce the secretion of cytokines. HSPs are also important in the induction, proliferation, suppressive function, and cytokine production of Tregs, which are a subset of CD4+ T cells maintaining peripheral tolerance. Together HSPs and Tregs are potential tools for future clinical interventions in autoimmune disease.
REFERENCES (92)
1.
Kampinga HH, Hageman J, Vos MJ, et al. (2009): Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14: 105-111.
2.
Houry WA (2001): Chaperone-assisted protein folding in the cell cytoplasm. Curr Protein Pept Sci 2: 227-244.
3.
van Eden W, van der Zee R, Prakken B (2005): Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5: 318-330.
4.
Young JC, Agashe VR, Siegers K, Hartl FU (2004): Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Mol Cell Biol 5: 781-791.
5.
Workman CJ, Szymczak-Workman AL, Collison LW, et al. (2009): The development and function of regulatory T cells. CMLS 66: 2603-2622.
6.
McHugh RS, Whitters MJ, Piccirillo CA, et al. (2002): CD4+CD25+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoidinduced TNF receptor. Immunity 16: 311-323.
7.
Kumanogoh A, Wang X, Lee I, et al. (2001): Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J Immunol 166: 353-360.
8.
Vignali DA, Collison LW, Workman CJ (2008): How regulatory T cells work. Nat Rev Immunol 8: 523–532.
9.
Sakaguchi S (2005): Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and nonself. Nat Immunol 6: 345-352.
10.
Gibson DJ, Elliott L, McDermott E, et al. (2015): Heightened Expression of CD39 by regulatory T lymphocytes is associated with therapeutic remission in inflammatory bowel disease. Inflamm Bowel Dis 21: 2806-2814.
11.
Ohta A, Sitkovsky M (2014): Extracellular adenosine-mediated modulation of regulatory T cells. Front Immunol 5: 304.
12.
Grossman WJ, Verbsky JW, Barchet W, et al. (2004): Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 21: 589-601.
13.
Thornton AM, Shevach EM (1998): CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 188: 287-296.
14.
Miyara M, Sakaguch S (2007): Natural regulatory T cells mechanisms of suppression. Trends Mol Med 13: 108-116.
15.
Scheffold A, Hühn J, Höfer T (2005): Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur J Immunol 35: 1336-1341.
16.
Jin B, Sun T, Yu XH, et al. (2012): The effects of TLR activation on T-cell development and differentiation. Clin Dev Immunol 2012: 836485.
17.
Chen T, Cao X (2010): Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunity. Eur J Immunol 40: 1541-1544.
18.
Wang Y, Seidl T, Whittall T, et al. (2010): Stress-activated dendritic cells interact with CD4+ T cells to elicit homeostatic memory. Eur J Immunol 40: 1628-1638.
19.
Stelter F (2000): Structure/function relationships of CD14. Chem Immunol 74: 25-41.
20.
Hoshino K, Takeuchi O, Kawai T, et al. (1999): Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162: 3749-3752.
21.
Martin CA, Carsons SE, Kowalewski R, et al. (2003): Aberrant extracellular and dendritic cell (DC) surface expression of heat shock protein (Hsp)70 in the rheumatoid joint: possible mechanisms of Hsp/DC-mediated cross-priming. J Immunol 171: 5736-5742.
22.
Rane MJ, Pan Y, Singh S, et al. (2003): Heat shock protein 27 controls apoptosis by regulating Akt activation. J Biol Chem 278: 27828-27835.
23.
Li Y, Zhang T, Schwartz SJ, Sun D (2009): New developments in Hsp90 inhibitors as anti-cancer therapeutics: mechanisms, clinical perspective and more potential. Drug Resist Updat 12: 17-27.
24.
Friedland JS, Shattock R, Remick DG, Griffin GE (1993): Mycobacterial 65-kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells. Clin Exp Immunol 91: 58-62.
25.
Retzlaff C, Yamamoto Y, Hoffman PS, et al. (1994): Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. Infect Immun 62: 5689-5693.
26.
Asea A, Kraeft SK, Kurt-Jones EA, et al. (2000): HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6: 435-442.
27.
DeMeester SL, Buchman TG, Cobb JP (2001): The heat shock paradox: does NF-kappaB determine cell fate? FASEB J 15: 270-274.
28.
Binder RJ, Han DK, Srivastava PK (2000): CD91: a receptor for heat shock protein gp96. Nat Immunol 1: 151-155.
29.
Kol A, Lichtman AH, Finberg RW, et al. (2000): Cutting edge: heat shock protein (HSP) 60 activates the innate immu¬ne response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol 164: 13-17.
30.
Zügel U, Schoel B, Yamamoto S, et al. (1995): Crossrecognition by CD8 T cell receptor alpha beta cytotoxic T lymphocytes of peptides in the self and the mycobacterial Hsp60 which share intermediate sequence homology. Eur J Immunol 25: 451-458.
31.
Chen W, Syldath U, Bellmann K, et al. (1999): Human 60-kDa heat-shock protein: A danger signal to the innate immune system. J Immunol 162: 3212-3219.
32.
Breloer M, Dorner B, More SH, et al. (2001): Heat shock proteins as ‘danger signals:’ eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-gamma production in T cells. Eur J Immunol 31: 20.
33.
Żylicz M, Wawrzynow A (2001): Insights into the function of Hsp70 chaperones. IUBMB Life 51: 283-287.
34.
van Eden W, Spiering R, Femke B (2012): A case of mistaken identity: HSPs are no DAMPs but DAMPERs. Cell Stress and Chaperones 17: 281-292.
35.
Marzec Ł, Zdrojewski Z, Bryl E (2007): Białko szoku termicznego 72(Hsp72) w chorobach nerek. Nefrol Dial Pol 11: 78-82.
36.
Garrido C, Gurbuxani S, Ravagnan L, Kroemer G (2001): Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem Biophys Res Commun 286: 433-442.
37.
Asea A (2005): Stress proteins and initiation of immune response: chaperokine activity of Hsp72. lmmunol Rev 11: 34-43.
38.
Johnson JD, Fleshner M (2006): Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72. J Leukoc Biol 79: 425-434.
39.
Tsan MF, Gao B (2009): Heat shock proteins and immune system. J Leukoc Biol 85: 905-910.
40.
Srivastava P (2002): Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20: 395-425.
41.
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 con¬troversial finding will go! Dedicated to Ferruccio Ritossa. Cell Stress Chaperones 16: 235-249.
42.
Faure O, Graff-Dubois S, Bretaudeau L, et al. (2004): Inducible Hsp70 as target of anticancer immunotherapy: identifica-tion of HLA-A*0201-restricted epitopes. Int J Cancer 108: 863-870.
43.
Bausero MA, Gastpar R, Multhoff G, Asea A (2005): Alternative mechanism by which IFN-g enhances tumor recognition: active release of heat shock protein 72. J Immunol 175: 2900-2912.
44.
Powers MV, Workman P (2006): Targeting of multiple signaling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr Relat Cancer 13 (Suppl 1): 125-135.
45.
Daugaard M, Rohde M, Jaattela M (2007): The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett 581: 3702-3710.
46.
Brunet M, Frisan E, Solary E, et al. (2008): Heat shock proteins: essential proteins for apoptosis regulation. J Cell Mol Med 12: 743-761.
47.
Chen D, Androlewicz MJ (2001): Heat shock protein 70 moderately enhances peptide binding and transport by transporter associated with antigen processing. Immunol Lett 75: 143-148.
48.
Doody AD, Kovalchin JT, Mihalyo MA, et al. (2004): Glycoprotein 96 can chaperone both MHC class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8+ T cell effector function. J Immunol 172: 6087-6092.
49.
Mycko MP, Cwiklinska H., Szymanski J, et al. (2004): Inducible heat shock protein 70 promotes myelin autoantigen presentation by the HLA class II. J Immunol 172: 202-213.
50.
SenGupta D, Norris PJ, Suscovich T J, et al. (2004): Heat shock protein-mediated crosspresentation of exogenous HIV antigen on HLA class I and class II. J Immunol 173: 1987-1993.
51.
Rajagopal D, Bal V, Mayor S, et al. (2006): A role for the Hsp90 molecular chaperone family in antigen presentation to T lymphocytes via major histocompatibility complex class II molecules. Eur J Immunol 36: 828-841.
52.
Lundberg K, Wegner N, Yucel-Lindberg T, Venables PJ (2010): Periodontitis in RA-the citrullinated enolase connection. Nat Rev Rheumatol 6: 727-730.
53.
Tukaj S, Kotlarz A, Jozwik A, et al. (2010): Hsp40 proteins modulate humoral and cellular immune response in rheumatoid arthritis patients. Cell Stress Chaperones 15: 555-566.
54.
Koffeman EC, Genovese M, Amox D, et al. (2009): Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial. Arthritis Rheum 60: 3207-3216.
55.
de Kleer IM, Wedderburn LR, Taams LS, et al. (2004): CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 172: 6435–6443.99.
56.
Prakken BJ, Roord S, Ronaghy A, et al. (2003): Heat shock protein 60 and adjuvant arthritis: a model for T cell regulation in human arthritis. Springer Semin Immunopathol 25: 47-63.
57.
Tukaj S, Lipińska B (2011): Białka szoku termicznego w reumatoidalnym zapaleniu stawów: przyjaciel czy wróg? Postepy Hig Med Dosw 65: 427-436.
58.
Kim MG, Jung Cho E, Won Lee J, et al. (2014): Tregs contribute to HSP70-induced renoprotective effect is partially mediated by CD4+CD25+Foxp3+ regulatory T cells in ischemia/reperfusion-induced acute kidney injury. Kidney Int 85: 62-71.
59.
Hakamada-Taguchi R, Uehara Y (2003): Inhibition of hydroxymethylglutaryl-coenzyme areductase reduces Th1 development and promotes Th2 development. Circ Res 93: 948-956.
60.
Ghayour-Mobarhan M, Lamb DJ (2005): Heat shock protein antibody titers are reduced by statin therapy in dyslipidemic subjects: a pilot study. Angiology 56: 61-68.
61.
Mercier PA, Winegarden NA, Westwood JT (1999): Human heat shock factor is predominantly a nuclear protein before and after heat stress. J Cell Sci 112: 2765-2769.
62.
Hansson GK (2005): Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352: 1685-1695.
63.
Hansson GK (2002): Vaccination against atherosclerosis: science or fiction? Circulation 106: 1599-1601.
64.
Ramos CH, Ferreira ST (2005): Protein folding, misfolding, and aggregation: evolving concepts and conformational diseases. Protein Pept Lett 12: 213-222.
65.
Gupta S (2012): Immunotherapies in diabetes mellitus type 1. Med Clin North Am 96: 621-634.
66.
Pugliese A (2012): The multiple origins of Type 1 diabetes. Diabet Med 10: 12081.
67.
Elias D, Marcus H, Reshef T, et al. (1995): Induction of diabetes in standard mice byimmunization with the p277 peptide of a 60-kDa heat shock protein. Eur J Immunol 25: 2851-2857.
68.
Birk OS, Elias D, Weiss AS, et al. (1996): NOD mouse diabetes: the ubiquitous mouse Hsp60 is a beta-cell target antigen of autoimmune T cells. J Autoimmun 9: 159-166.
69.
Horvath L, Cervenak L, Oroszlan M, et al. (2002): Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus. Immunol Lett 80: 155-162.
70.
Sobel DO, Creswell K (2006): Characterization of anti-islet cytotoxic human T-cell clones from patients with type 1 diabetes mellitus. Autoimmunity 39: 323-332.
71.
Marek-Trzonkowska N, Myśliwec M, Siebert J, Trzonkowski P (2013): Clinical application of regulatory T cells in type 1 diabetes. Pediatr Diabetes 14: 322-332.
72.
Raz I, Avron A, Tamir M, et al. (2007): Treatment of new-onset type 1 diabetes with peptide DiaPep277 is safe and associated with preserved beta-cell function: extension of a randomized, double-blind, phase II trial. Diabetes Metab Res Rev 23: 292-298.
73.
Raz I, Elias D, Avron A, et al. (2001): Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. Lancet 358: 1749-1753.
74.
Huurman VA, Decochez K, Mathieu C, et al. (2007): Therapy with the Hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients. Diabetes Metab Res Rev 23: 269-275.
75.
Massa M, Passalia M, Manzoni SM, et al. (2007): Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis. Arthritis Rheum 56: 1648-1657.
76.
Zanin-Zhorov (2006): Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling. J Clin Invest 116: 2022-2032.
77.
Samsom JN (2004): Regulation of antigen-specific regulatory T-cell induction via nasal and oral mucosa. Crit Rev Immunol 24: 157-177.
78.
Sutmuller R, Garritsen A, Adema GJ (2007): Regulatory T cells and toll-like receptors: regulating the regulators. Ann Rheum Dis 66: 91-95.
79.
de Kleer IM, Kamphuis SM, Rijkers GT, et al. (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.
80.
Marcenaro E, Carlomagno S, Pesce S, et al. (2011): Bridging Innate NK Cell Functions with Adaptive Immunity. Adv Exp Med Biol 780: 45-55.
81.
Aalberse JA, Kapitein B, deRoock S (2011): Cord blood CD4+ T cells respond to self heat shock protein 60 (HSP60). PLoS One 6.
82.
Wachstein, Tischer S, Figueiredo C, et al. (2012 ): HSP70 enhances immunosuppressive function of CD4+CD25+FoxP3+ T regulatory cells and cytotoxicity in CD4+CD25- T cells. PLoS One 7.
83.
de Zoeten EF, Wang L, Sai H, et al. (2010): Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. Gastroenterology 138: 583-594.
84.
Tanaka S, Kimura Y, Mitani A, et al. (1999): Activation of T cells recognizing an epitope of heat-shock protein 70 can protect against rat adjuvant arthritis. J Immunol 163: 5560-5565.
85.
Bloemendal A, Van der Zee R, Rutten VP, et al. (1997): Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (Hsp) 60 and Hsp70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthritis (RA). Clin Exp Immunol 110: 72-78.
86.
Kingston AE, Hicks CA, Colston MJ, Billingham ME (1996): A 71-kD heat shock protein (Hsp) from Mycobacterium tuberculosis has modulatory effects on experimental rat arthritis. Clin Exp Immunol 103: 77-82.
87.
Prakken BJ, Wendling U, van der Zee R, et al. (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.
88.
Wendling U, Paul L, van der Zee R, et al. (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.
89.
van Eden W, Hauet-Broere F, Berlo S, et al. (2005): Stress proteins as inducers and targets of regulatory T cells in arthritis. Int Rev Immunol 24: 181-197.
90.
van Herwijnen MJ, Wieten L, van der Zee R, et al. (2012): Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune. Proc Natl Acad Sci U S A 109: 14134-14139.
91.
Aoyagi S, Archer TK (2005): Modulating molecular chaperone Hsp90 functions through reversible acetylation. Trends in Cell Biology 15: 565-567.
92.
de Zoeten EF, Wang L, Butler K, et al. (2011): Histone Deacetylase 6 and Heat Shock Protein 90 Control the functions of Foxp3+ T-Regulatory Cells. Mol Cell Biol 10: 2066-2078.
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