Trends in Immunology
Volume 26, Issue 11, November 2005, Pages 613-618
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Autoimmunity special issue
NK cells: elusive players in autoimmunity

https://doi.org/10.1016/j.it.2005.08.008Get rights and content

Natural killer (NK) cells were once regarded as relatively simple cells of the innate immune system. However, they are now revealing themselves as multifunctional regulatory cells that are present throughout the body. The role of NK cells in autoimmunity is attracting increased attention, although the picture is clouded by a conflicting literature that presents disease-promoting as well as disease-protective roles. In this review, we discuss how NK cells might use these dual roles, and suggest that future studies should focus on the impact of the anatomical localization of NK cells as well as the cytokine environment in which NK cells act in individual autoimmune diseases.

Section snippets

Natural killer (NK) cells

NK cells mediate early protection against viruses, kill cancer cells, rid the body of antibody-coated cells and secrete cytokines, predominantly interferon-γ (IFN-γ) [1]. NK cells are related developmentally to T cells [2] but differ from T cells in that they do not express one single variable receptor but rely on a multitude of germline-encoded receptors for their specificity 3, 4. In addition, NK cells are thymus-independent and do not require pre-immunization to act but are ready to go on

NK cells in autoimmune diseases – protective or pathogenic?

The studies that have been performed point towards both protective and disease-promoting effects of NK cells, depending on the disease model.

NK cells as adaptive multicompetent players in autoimmunity

It is clear from the specific studies outlined earlier that NK cells can be both protective and pathogenic in different disease models, and sometimes even in the same model, such as EAE 13, 14, 24 and diabetes 21, 29. Two aspects of NK-cell biology might provide explanations for these opposing effects. The first deals with the possible functional differences between NK cells at different anatomical localizations and the second with the adaptability, or flexibility, of effector responses in NK

Future work

Although the adaptive arms of immunity are known culprits in autoimmunity, future studies will probably show a similarly important role for innate cells, including NK cells, in these responses. Regarding NK cells, the current picture is complex and contains images of both disease-promoting and disease-preventing roles (Figure 1). Difficulties in understanding discrepancies in the role of NK cells in autoimmunity might lie in our incomplete understanding of the in vivo biology of NK cells, as

Acknowledgements

Work in our laboratory is supported by the Swedish Research Council, the Swedish Cancer Society, the Clas Groshinsky Memory Foundation, the Swedish Medical Doctor's Association, the Human Frontiers Science Foundation and the Swedish Foundation for Strategic Research. This work was performed within IRIS, a strategic research center sponsored by the Swedish Foundation for Strategic Research.

References (70)

  • B.R. Lauwerys

    Synergistic proliferation and activation of natural killer cells by interleukin 12 and interleukin 18

    Cytokine

    (1999)
  • H. Chakir

    Cytokine expression by murine DX5+ cells in response to IL-12, IL-18, or the combination of IL-12 and IL-18

    Cell. Immunol.

    (2001)
  • D.A. Horwitz

    Role of NK cells and TGF-β in the regulation of T-cell-dependent antibody production in health and autoimmune disease

    Microbes Infect.

    (1999)
  • B. Perussia

    Peripheral NK cell phenotypes: multiple changing of faces of an adapting, developing cell

    Mol. Immunol.

    (2005)
  • M.A. Cooper

    The biology of human natural killer-cell subsets

    Trends Immunol.

    (2001)
  • K. Ogasawara

    Impairment of NK cell function by NKG2D modulation in NOD mice

    Immunity

    (2003)
  • Y. Suzuki

    Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to Psoriasis vulgaris

    J. Invest. Dermatol.

    (2004)
  • W.M. Yokoyama

    The dynamic life of natural killer cells

    Annu. Rev. Immunol.

    (2004)
  • E.E. Rosmaraki

    Identification of committed NK cell progenitors in adult murine bone marrow

    Eur. J. Immunol.

    (2001)
  • L.L. Lanier

    NK Cell Recognition

    Annu. Rev. Immunol.

    (2005)
  • F. Colucci

    Natural killer cell activation in mice and men: different triggers for similar weapons?

    Nat. Immunol.

    (2002)
  • M. Kronenberg

    Toward an understanding of NKT cell biology: progress and paradoxes

    Annu. Rev. Immunol.

    (2005)
  • C. Carnaud

    Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells

    J. Immunol.

    (1999)
  • I. Andre

    Checkpoints in the progression of autoimmune disease: lessons from diabetes models

    Proc. Natl. Acad. Sci. U. S. A.

    (1996)
  • K. Takahashi

    The regulatory role of natural killer cells in multiple sclerosis

    Brain

    (2004)
  • K. Takahashi

    Natural killer type 2 bias in remission of multiple sclerosis

    J. Clin. Invest.

    (2001)
  • B. Zhang

    Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells

    J. Exp. Med.

    (1997)
  • Y. Matsumoto

    Role of natural killer cells and TCR γδ T cells in acute autoimmune encephalomyelitis

    Eur. J. Immunol.

    (1998)
  • R.B. Smeltz

    Inhibition of autoimmune T cell responses in the DA rat by bone marrow-derived NK cells in vitro: implications for autoimmunity

    J. Immunol.

    (1999)
  • R. Watanabe-Fukunaga

    Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis

    Nature

    (1992)
  • A. Yabuhara

    A killing defect of natural killer cells as an underlying immunologic abnormality in childhood systemic lupus erythematosus

    J. Rheumatol.

    (1996)
  • F. Erkeller-Yusel

    Lymphocyte subsets in a large cohort of patients with systemic lupus erythematosus

    Lupus

    (1993)
  • K. Takeda et al.

    The development of autoimmunity in C57BL/6 lpr mice correlates with the disappearance of natural killer type 1-positive cells: evidence for their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms

    J. Exp. Med.

    (1993)
  • I.F. Lee

    Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK cells

    J. Immunol.

    (2004)
  • D.J. Todd

    Deficiencies in gut NK cell number and function precede diabetes onset in BB rats

    J. Immunol.

    (2004)
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