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Cited by 439Immunotherapy and Immune ResponsesImmune Response and InflammationImmune responses and vaccinations

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Altered Innate Immune Functioning of Dendritic Cells in Elderly Humans: A Role of Phosphoinositide 3-Kinase-Signaling Pathway

Agrawal, Anshu, Agrawal, Sudhanshu, Cao, Jia-Ning, Su, Houfen, Osann, Kathryn, Gupta, Sudhir·2007·The Journal of Immunology
DOI 10.4049/jimmunol.178.11.6912
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Abstract

Aging represents a state of paradox where chronic inflammation is associated with declining immune responses. Dendritic cells (DCs) are the major APCs responsible for initiating an immune response. However, DC functions in aging have not been studied in detail. In this study, we have compared the innate immune functions of monocyte-derived myeloid DCs from elderly subjects with DCs from young individuals. We show that although phenotypically comparable, DCs from the aging are functionally different from DCs from the young. In contrast to DCs from the young, DCs from elderly individuals display 1) significantly reduced capacity to phagocytose Ags via macropinocytosis and endocytosis as determined by flow cytometry; 2) impaired capacity to migrate in vitro in response to the chemokines MIP-3β and stromal cell-derived factor-1; and 3) significantly increased LPS and ssRNA-induced secretion of TNF-α and IL-6, as determined by ELISA. Investigations of intracellular signaling revealed reduced phosphorylation of AKT in DCs from the aging, indirectly suggesting decreased activation of the PI3K pathway. Because the PI3K-signaling pathway plays a positive regulatory role in phagocytosis and migration, and also functions as a negative regulator of TLR signaling by inducing activation of p38 MAPK, this may explain the aberrant innate immune functioning of DCs from elderly subjects. Results from real-time PCR and protein expression by flow cytometry demonstrated an increased expression of phosphatase and tensin homolog, a negative regulator of the PI3K-signaling pathway, in DCs from the aging. Increased phosphatase and tensin homolog may thus be responsible for the defect in AKT phosphorylation and, therefore, the altered innate immune response of DCs from elderly humans.

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Research works printed but not linked: 63

  1. 2003, Microbes Infect., 1279
  2. 1997, Exp. Gerontol., 401
  3. 1998, Mech. Ageing Dev., 11
  4. 2004, J. Immunol., 3437
  5. 2001, Curr. Opin. Hematol., 131
  6. 2004, Ann. NY Acad. Sci., 104
  7. 1999, Acta. Neurol. Scand., 34
  8. 1992, Life Sci., 1953
  9. 1998, Front. Biosci., d59
  10. 2004, Nat. Immunol., 133
  11. 1996, J. Exp. Med., 1891
  12. 2003, Proc. Natl. Acad. Sci. USA, 15053
  13. 1997, Immunol. Rev., 79
  14. 1999, Exp. Gerontol., 7
  15. 1992, Mech. Ageing Dev., 57
  16. 2004, Exp. Gerontol., 545
  17. 2003, Biochem. Soc. Trans., 447
  18. 2002, Semin. Immunol., 267
  19. 1991, Annu. Rev. Immunol., 271
  20. 1998, Nature, 245
  21. 2000, Annu. Rev. Immunol., 767
  22. 2001, Nat. Immunol., 947
  23. 2001, Science, 253
  24. 1997, Eur. J. Immunol., 3135
  25. 2003, J. Immunol., 4984
  26. 2002, J. Biol. Chem., 32124
  27. 2003, Trends Immunol., 358
  28. 2002, Nat. Immunol., 875
  29. 2003, Blood, 3560
  30. 1995, J. Exp. Med., 389
  31. 1995, FEBS Lett., 272
  32. 1996, J. Cell Biol., 1249
  33. 2003, Semin. Immunol., 271
  34. 2005, Nat. Rev. Immunol., 617
  35. 1999, J. Immunol., 3859
  36. 2004, EMBO J., 3505
  37. 2000, Immunol. Rev., 217
  38. 2002, Immunology, 125
  39. 1999, Proc. Natl. Acad. Sci. USA, 4240
  40. 2001, Exp. Cell Res., 29
  41. 2000, Cell, 87
  42. 1999, Trends Cell Biol., 125
  43. 1998, J. Biol. Chem., 13375
  44. 1996, Genes Dev., 1084
  45. 2000, Vaccine, 1606
  46. 1996, Clin. Exp. Immunol., 544
  47. 1987, Mech. Ageing Dev., 69
  48. 1990, J. Invest. Dermatol., 247
  49. 2002, Scand. J. Immunol., 518
  50. 1995, Eur. J. Immunol., 1319
  51. 2000, Exp. Gerontol., 213
  52. 1993, Eur. J. Immunol., 2375
  53. 2006, J. Gerontol. A Biol. Sci. Med. Sci., 1039
  54. 2002, J. Immunol., 4697
  55. 1998, J. Clin. Invest., 890
  56. 2000, J. Exp. Med., 423
  57. 2002, Immunology, 466
  58. 2005, Immunol. Rev., 207
  59. 2006, Nat. Rev. Genet., 606
  60. 2006, Immunol. Res., 33
  61. 2003, J. Immunol., 717
  62. 1999, Proc. Natl. Acad. Sci. USA, 6199
  63. 2003, Trends Cell Biol., 478

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Metadata

Authors
Agrawal, A., Agrawal, S., Cao, J.-N., Su, H., Osann, K., & Gupta, S.
Affiliations
  • University of California, Irvine (US)
  • Division of Basic and Clinical Immunology, University of California , Irvine, CA 92697
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2007-06-01
Volume
178
Issue
11
Pages
6912-6922
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.178.11.6912
OpenAlex
W1508177354
Cited by
435
References
64
Citations by year
2026: 10 · 2025: 20 · 2024: 20 · 2023: 18 · 2022: 20 · 2021: 20 · 2020: 33 · 2019: 28 · 2018: 29 · 2017: 26 · 2016: 22 · 2015: 22 · 2014: 28 · 2013: 34 · 2012: 21
FWCI
8.05
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of California, Irvine
  • National Institute on Aging (AG-027512, R21AG027512)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
dendritic cells, aging, innate immunity, phosphoinositide 3-kinase signaling, Akt phosphorylation, phagocytosis, dendritic cell migration, chemokines, CCL19, CXCL12, TNF-α, interleukin-6, lipopolysaccharide, phosphatase and tensin homolog, chronic inflammation, p38 MAPK, Toll-like receptor signaling
MeSH terms
Phosphoinositide-3 Kinase Inhibitors, Adult, Aged, Aged, 80 and over, Aging, Cell Count, Cell Differentiation, Cells, Cultured, Dendritic Cells, Humans, Immunity, Innate, Monocytes, Signal Transduction, Up-Regulation, Cytokines, Inflammation Mediators, Jurkat Cells, Phosphatidylinositol 3-Kinases, PTEN Phosphohydrolase

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