Cytokines

Abstract

Cytokines are small secreted ‘messenger proteins’ that allow communication between cells. They contribute to a chemical signalling language that controls many processes in multicellular organisms, including haematopoiesis, chemoattraction, tissue repair, embryogenesis and virtually all aspects of immunity and inflammation. Cytokine functions are mediated by their binding to specific receptors to initiate intracellular signalling cascades that increase or decrease expression of transcription factors and genes regulating, for example secretion of effector molecules (including other cytokines), cell proliferation and expression of membrane receptors. They play an important role in many pathologies, and indeed measurement of cytokine profiles in patients can provide a useful indicator of disease. Owing to their multiple functions in disease, therapeutic interference with cytokines, cytokine receptors or their signal transduction pathways offers new treatment options for a range of disorders.

Key Concepts

  • Cytokines can be extremely potent, acting at picomolar or femtomolar concentrations.
  • Cytokines are not produced constitutively but are expressed on stimulation of cells, usually acting in an autocrine or paracrine fashion.
  • Individual cytokines can have many functions and can act synergistically or antagonistically.
  • Chemokines are a family of cytokines that are not only principally involved in chemoattraction but also participate in cell activation and angiogenesis.
  • Different cytokine receptors can share similar subunit structures, which divide them into families.
  • Most cytokine receptors are heterodimers, but some can be homodimers or heterotrimers.
  • Cytokines exert their effects by activating specific intracellular signalling pathways.
  • By sharing receptor subunits and signal‐transducing molecules, many cytokines are known to play redundant and pleiotropic roles.
  • Excessive or defective cytokine production or activity can lead to several pathologies, and cytokine modifiers are proving to be a therapeutically effective approach in modifying such diseases.
  • Cytokine synthesis and activity are regulated by many mechanisms including signalling inhibitors, epigenetic modifications and cleavage of precursors.

Keywords: cytokines; chemokines; cytokine receptors; cytokine signalling; cytokine/anticytokine therapy

Figure 1. Receptors for different cytokines are classified into families on the basis of conserved extracellular domain structures and signalling mechanisms. WSXWS, tryptophan‐serine‐X‐tryptophan‐serine.
Figure 2. Differentiation of main CD4+ T helper cells. This figure illustrates the importance of cytokines in directing polarisation and determining functional activity. Key transcription factors are shown in (brackets).
Figure 3. Factors determining cytokine secretion and activity.
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Further Reading

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Wilson, Heather M, and Barker, Robert N(Jun 2020) Cytokines. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000929.pub4]