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Published in:

01-01-2008

Biology of Dendritic Cells in Aging

Authors: Anshu Agrawal, Sudhanshu Agrawal, Jia Tay, Sudhir Gupta

Published in: Journal of Clinical Immunology | Issue 1/2008

Abstract

Dendritic cells are central to the generation of both immunity and tolerance. This review focuses on the alterations in the functions of dendritic cells in aged and its consequences on both tolerance and immunity. We have discussed certain mechanisms responsible for the defective dendritic cell function associated with aging.

Boren E, Gershwin ME. Inflamm-aging: autoimmunity, and the immune-risk phenotype. Autoimmun Rev 2004;3:401–6.PubMedCrossRef

Weyand CM, Fulbright JW, Goronzy JJ. Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp Gerontol 2003;38:833–41.PubMedCrossRef

Ramos-Casals M, Garcia-Carrasco M, Brito MP, Lopez-Soto A, Font J. Autoimmunity and geriatrics: clinical significance of autoimmune manifestations in the elderly. Lupus 2003;12:341–55.PubMedCrossRef

Bruunsgaad H, Pedersen BK. Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am 2003;23:15–39.CrossRef

Ginaldi L, De Martinis M, Monti D, Franceschi C. The immune system in the elderly: activation-induced and damage-induced apoptosis. Immunol Res 2004;30:81–94.PubMedCrossRef

Miller RA. The aging immune system: primer and prospectus. Science 1996;273:70–4.PubMedCrossRef

Linton PJ, Haynes L, Klinman NR, Swain SL. Antigen-independent changes in naive CD4 T cells with aging. J Exp Med 1996;184:1891–900.PubMedCrossRef

Pawalec G, Remarque E, Barnett Y, Solana R. T cells and aging. Front Biosci 1998;3:d59–99.

Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol 2004;5:133–9.PubMedCrossRef

10.

Haynes L, Eaton SM, Burns EM, Randall TD, Swain SL. CD4 T cell memory derived from young naïve cells functions well into old age, while memory generated from aged naïve cells functions poorly. Proc Natl Acad Sci USA 2003;100:15053–8.PubMedCrossRef

11.

Gupta S, Bi R, Su K, Yel L, Chiplunkar S, Gollapudi S. Characterization of naive, memory and effector CD8+ T cells: effect of age. Exp Gerontol 2004;39:545–50.PubMedCrossRef

12.

Dunn-Walters DK, Banerjee M, Mehr R. Effects of age on antibody affinity maturation. Biochem Soc Trans 2003;31:447–8.PubMedCrossRef

13.

Wick G, Grubeck-Loebenstein B. The aging immune system: primary and secondary alterations of immune reactivity in the elderly. Exp Gerontol 1997;32:401–13.PubMedCrossRef

14.

McGlauchlen KS, Vogel LA. Ineffective humoral immunity in the elderly. Microbes Infect 2003;5:1279–84.PubMedCrossRef

15.

Ernst DN, Weigle WO, Noonan DJ, McQuitty DN, Hobbs MV. The age-associated increase in IFN-gamma synthesis by mouse CD8⁺ T cells correlates with shifts in the frequencies of cell subsets defined by membrane CD44, CD45RB, 3G11, and MEL-14 expression. J Immunol 1993;151:575–87.PubMed

16.

Kubo M, Cinader B. Polymorphism of age-related changes in interleukin (IL) production. Differential changes of T helper subpopulations, synthesizing IL 2, IL 3 and IL 4. Eur J Immunol 1990;20:1289–96.PubMedCrossRef

17.

Thoman ML, Weigle WO. Cell-mediated immunity in aged mice: an underlying lesion in IL 2 synthesis. J Immunol 1982;128:2358–61.PubMed

18.

Gupta S, Su H, Bi R, Gollapudi S. Differential sensitivity of naïve and memory subsets of human CD8+ T cells to TNF-alpha-induced apoptosis. J Clin Immunol 2006;26:193–203.PubMedCrossRef

19.

Gupta S, Gollapudi S. TNF-alpha-induced apoptosis in human naïve and memory CD8+ T cells in aged humans. Exp Gerontol 2006;41:69–77.PubMedCrossRef

20.

Posnett DN, Yarilin D, Valiando JR, Li F, Liew FY, Weksler ME, et al. Oligoclonal expansions of antigen-specific CD8+ T cells in aged mice. Ann N Y Acad Sci 2003;987:274–9.PubMedCrossRef

21.

Banchereau J, Steinman RM. Dendritic cells and the control of immunity [review]. Nature 1998;392:245–52.PubMedCrossRef

22.

Cella M, Sallusto F, Lanzavecchia A. Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 1997;9:10–6.PubMedCrossRef

23.

Inaba K, Metlay JP, Crowley MT, Steinman RM. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med 1990;172:631–40.PubMedCrossRef

24.

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.PubMedCrossRef

25.

Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells [review]. Annu Rev Immunol 2003;21:685–711.PubMedCrossRef

26.

Wu L, Liu YJ. Development of dendritic-cell lineages. Immunity 2007;26:741–50.PubMedCrossRef

27.

Grolleau-Julius A, Garg MR, Mo R, Stoolman LL, Yung RL. Effect of aging on bone marrow-derived murine CD11c+CD4-CD8alpha-dendritic cell function. J Gerontol A Biol Sci Med Sci 2006;61:1039–47.PubMed

28.

Tesar BM, Walker WE, Unternaehrer J, Joshi NS, Chandele A, Haynes L, et al. Murine [corrected] myeloid dendritic cell-dependent toll-like receptor immunity is preserved with aging. Aging Cell 2006;5:473–86. Erratum in: Aging Cell 2007;6:129.PubMedCrossRef

29.

Agrawal A, Agrawal S, Gupta S. Dendritic cells in human aging. Exp Gerontol 2006;42:421–6.PubMedCrossRef

30.

Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, et al. Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 2007;122:220–8.PubMedCrossRef

31.

Shodell M, Siegal FP. Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing. Scand J Immunol 2002;56:518–21.PubMedCrossRef

32.

Agrawal A, Agrawal S, Jianing Cao, Houfen Su, Kathryn Osann, Gupta S. Altered innate immune functioning of dendritic cells in aging humans: role of PI3Kinase signaling pathway. J Immunol 2007;178:6912–22.PubMed

33.

Lung TL, Saurwein-Teissl M, Parson W, Schonitzer D, Grubeck-Loebenstein B. Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 2000;18:1606–12.PubMedCrossRef

34.

Steger MM, Maczek C, Grubeck-Loebenstein B. Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals. Clin Exp Immunol 1996;105:544–50.PubMedCrossRef

35.

Kurban RS, Bhawan J. Histologic changes in skin associated with aging. J Dermatol Surg Oncol 1990;16:908–14.PubMed

36.

Steuhl KP, Sitz U, Knorr M, Thanos S, Thiel HJ. Age-dependent distribution of Langerhans cells within human conjunctival epithelium. Ophthalmologe 1995;92:21–5.PubMed

37.

Indrasingh, Chandi G, Jevaseelan L, Vettivel S, Chandi SM. Quantitative analysis of CD1a (T6) positive Langerhans cells in human tonsil epithelium. Anat Anz 1999;181:567–72.CrossRef

38.

Zavala WD, Cavicchia JC. Deterioration of the Langerhans cell network of the human gingival epithelium with aging. Arch Oral Biol 2006;51:1150–5.PubMedCrossRef

39.

Gilchrest BA, Murphy GF, Soter NA. Effect of chronologic aging and ultraviolet irradiation on Langerhans cells in human epidermis. J Invest Dermatol 1989;79:85–8.CrossRef

40.

Thiers BH, Maize JC, Spicer SS, Cantor AB. The effect of aging and chronic sun exposure on human Langerhans cell populations. J Invest Dermatol 1984;82:223–6.PubMedCrossRef

41.

Choi KL, Sauder DN. Epidermal Langerhans cell density and contact sensitivity in young and aged BALB/c mice. Mech Ageing Dev 1987;39:69–79.PubMedCrossRef

42.

Sprecher E, Becker Y, Kraal G, Hall E, Harrison D, Shultz LD. Effect of aging on epidermal dendritic cell populations in C57BL/6J mice. J Invest Dermatol 1990;94:247–53.PubMedCrossRef

43.

Fujihashi K, McGhee JR. Mucosal immunity and tolerance in the elderly. Mech Ageing Dev 2004;25:889–98.CrossRef

44.

Varas A, Sacedon R, Hernandez-Lopez C, Jimenez E, Garcia-Ceca J, Arias-Diaz J, et al. Age-dependent changes in thymic macrophages and dendritic cells. Microsc Res Tech 2003;62:501–7.PubMedCrossRef

45.

Stichel CC, Luebbert H. Inflammatory processes in the aging mouse brain: participation of dendritic cells and T-cells. Neurobiol Aging 2007;28:1507–21.PubMedCrossRef

46.

Sallusto F, Cella M, Danieli C, Lanzavecchia A. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med 1995;182:389–400.PubMedCrossRef

47.

Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 2001;194:769–79.PubMedCrossRef

48.

Steinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med 2000;191:411–6.PubMedCrossRef

49.

Wu X, Molinaro C, Johnson N, Casiano CA. Secondary necrosis is a source of proteolytically modified forms of specific intracellular autoantigens: implications for systemic autoimmunity. Arthritis Rheum 2001;44:2642–52.PubMedCrossRef

50.

Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 2000;191:423–34.PubMedCrossRef

51.

van Vliet SJ, Dunnen JD, Gringhuis SI, Geijtenbeek TB, van Kooyk Y. Innate signaling and regulation of Dendritic cell immunity. Curr Opin Immunol 2007; (Jul 11; in press).

52.

Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S. Cutting edge: impaired Toll-like receptor expression and function in aging. J Immunol 2002;169:4697–701.PubMed

53.

Gunn MD. Chemokine mediated control of dendritic cell migration and function. Semin Immunol 2003;15:271–6.PubMedCrossRef

54.

Kellermann SA, Hudak S, Oldham ER, Liu YJ, McEvoy LM. TheCCchemokine receptor-7 ligands 6Ckine and macrophage inflammatory protein 3 are potent chemoattractants for in vitro-and in vivo-derived dendritic cells. J Immunol 1999;162:3859–64.PubMed

55.

Forster R, Schubel A, Brietfeld D, Kremmer E, Renner-Muller I, Wolf E, et al. CCR-7 coordinates primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999;99:23–33.PubMedCrossRef

56.

Bhushan M, Cumberbatch M, Dearman RJ, Andrew SM, Kimber I, Griffiths CE. Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the influence of ageing. Br J Dermatol 2002;146:32–40.PubMedCrossRef

57.

Pietschmann P, Hahn P, Kudlacek S, Thomas R, Peterlik M. Surface markers and transendothelial migration of dendritic cells from elderly subjects. Exp Gerontol 2000;35:213–22.PubMedCrossRef

58.

Linton PJ, Li SP, Zhang Y, Bautista B, Huynh Q, Trinh T. Intrinsic versus environmental influences on T-cell responses in aging. Immunol Rev 2005;205:207–19.PubMedCrossRef

59.

Cumberbatch M, Dearman RJ, Kimber I. Influence of ageing on Langerhans cell migration in mice: identification of a putative deficiency of epidermal interleukin-1beta. Immunology 2002;105:466–77.PubMedCrossRef

60.

Dillon S, Agrawal A, Van Dyke T, Landreth G, McCauley L, Maliszewski C, et al. TLR2 AND TLR4 ligands stimulate distinct dendritic cell responses and adaptive immunity, by differential modulation of ERK MAP kinase and c-fos. J Immunol 2004;172:4733–43.PubMed

61.

Agrawal S, Agrawal A, Doughty B, Gerwitz A, Blenis J, Van Dyke T, et al. Cutting Edge: different TLR agonists instruct dendritic cells to induce distinct T-helper responses, via differential modulation of ERK MAP kinase and c-fos. J Immunol 2003;171:4984–9.PubMed

62.

Agrawal A, Kaushal P, Agrawal S, Gollapudi S, Gupta S. Thimerosal affects human dendritic cell functions promoting a TH2 response. J Leukoc Biol 2007;81:474–83.PubMedCrossRef

63.

Gutcher I, Becher B. APC-derived cytokines and T cell polarization in autoimmune inflammation. J Clin Invest 2007;117:1119–27.PubMedCrossRef

64.

Cua DJ, Sherlock J, Chen Y. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744–8.PubMedCrossRef

65.

Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201:233–40.PubMedCrossRef

66.

Haruna H, Inaba M, Inaba K, Taketani S, Sugiura K, Fukuba Y, et al. Abnormalities of B cells and dendritic cells in SAMP1 mice. Eur J Immunol 1995;25:1319–25.PubMedCrossRef

67.

Donnini A, Argentati K, Mancini R, et al. Phenotype, antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol 2002;37:1097–112.PubMedCrossRef

68.

Sharma S, Dominguez AL, Lustgarten J. Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB. Exp Gerontol 2006;41:78–84.PubMedCrossRef

69.

Grewe M. Chronological ageing and photoageing of dendritic cells. Clin Exp Dermatol 2001;26:608–12.PubMedCrossRef

70.

Araki N, Johnson MT, Swanson JA. A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol 1996;135:1249–60.PubMedCrossRef

71.

Clague MJ, Thorpe C, Jones AT. Phosphatidylinositol 3-kinase regulation of fluid phase endocytosis. FEBS Lett 1995;367:272–4.PubMedCrossRef

72.

Del Prete A, Vermi W, Dander E, Otero K, Barberis L, Luini W. Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice. EMBO J 2004;23:3505–15.PubMedCrossRef

73.

Fukao T, Koyasu S. PI3K and negative regulation of TLR signaling. Trends Immunol 2003;24:358–63.PubMedCrossRef

74.

Guha M, Mackman N. The PI3K-Akt pathway limits LPS activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 2002;277:32124–32.PubMedCrossRef

75.

Martin M, Schifferle RE, Cuesta N, Vogel SN, Katz J, Michalek SM. Role of the phosphatidylinositol 3 kinase-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J Immunol 2003;171:717–25.PubMed

76.

Agrawal A, Lingappa J, Leppa SH, Agrawal S, Jabbar A, Quinn C, et al. Impairement of dendritic cells and adaptive immunity by Anthrax lethal factor. Nature 2003;424:329–34.PubMedCrossRef

77.

Sun H, Lesche R, Li DM, Liliental J, Zhang H, Gao J, et al. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci USA 1999;96:6199–204.PubMedCrossRef

Title: Biology of Dendritic Cells in Aging
Authors: Anshu Agrawal
Sudhanshu Agrawal
Jia Tay
Sudhir Gupta
Publication date: 01-01-2008
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 1/2008
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-007-9127-6

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