Cytokines Atlas


Natural Killer (NK) Cells & Cytokines

Natural killer (NK) cells are lymphoid cells poised and ready to assist in the destruction of virally infected cells and tumor cells from the body. Unlike most lymphoid cells, NK cells are part of the innate immune system and mediate their effect in an antigen independent manner that in general does not give rise to immunological memory or protective immunity. NK cells become activated upon stimulation by the cytokines IL-2, IL-15, IL-15RA in complex with IL-15, IL-18 and IL-12 to produce a large variety of cytokines and chemokines that includes IFNγ, TNFα, IL-17 and IL-22 to name a few. Similar to cytolytic CD8+ T cells, NK cells contain a variety of proteins that mediate the destruction of target cells by inducing a program of apoptotic cell death. NK cells are characterized by the presence of cytoplasmic granules that contain proteins such as perforin and granzymes. Perforin creates holes in the target cell membrane and the granzymes move into the target cell to initiate the apoptotic process via the induction of caspases. Granzyme B is the most characterized, but others such as A through M, are also active in initiating the apoptotic process.

NK cells, although derived from the same lineage as T and B cells, do not express an antigen specific receptor such as a T cell receptor or a B cell receptor. However, to recognize their targets, NK cells are equipped with a battery of receptors that bind to specific components present at the surface of bacterias, virally-infected cells, stressed cells, or cancer cells. NK cells are characterized by the expression of CD56 (both high and low levels) and the KIR family receptors in humans and CD49b and Ly49 family members in mice. The repertoire of receptors can be activating or inhibiting thereby allowing a unique and strictly controlled response by the NK cell.

NK cells have been shown to play a beneficial role in suppressing graft-versus-host disease (GVHD) in animal models. In autoimmune disease, NK cells can have a dual role of disease-promoting and disease-controlling. Additionally, the role can change depending on the stage of the disease. Multiple sclerosis and systemic lupus erythematosus (SLE) studies indicate NK cells play a disease-controlling role.

NK Cell Differentiation Profile

Master Regulator of Differentiation

E4BP4

Stimulants to Mature/Activate

IL-2

  • Augments NK cell activity and boosts its cytolytic activity by activating various kinase pathways

IL-12

  • Induced activation, stimulates cytotoxicity and production of IFNγ and TNF

IL-15/IL-15R

  • Involved in proliferation, accumulation and survival

IL-18

  • Upregulates NK cell cytotoxicity

NK Cell Secreted Cytokine Profile

Granzyme B (as well as A - M)

  • Induces target cell death by apoptosis
    IFNγ
  • Inhibits proliferation of Th2 cells and enhances proliferation of activated B cells

IL-17A

  • Regulates local tissue inflammation

IL-22

  • Regulates the production of acute phase proteins

MIP-1α (CCL3)

  • Plays in recruitment of leukocytes, particularyly CD8+ T cells, to stimulate strong antigen specific responses

MIP-1β (CCL4)

  • Plays in recruitment of leukocytes, particularyly CD4+ T cells, to promote antibody response

Perforin

  • Creates holes in target cell membrane

RANTES (CCL5)

  • Initates leukocyte recruitment and is involved in proliferation and activation of certain cell types

TNFα

  • Involved in regulation of cell survival and pro-inflammatory properties

NK Cell Differentiation Profile

NK Cell Cytokines
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