Interleukin 17‐Producing T Lymphocytes

Abstract

IL‐17‐producing T lymphocytes (T17s) play important roles in the clearance of extracellular bacterial and fungal infections. T17s consist of several subsets of lymphocytes possessing both innate and adaptive immune phenotypes. The production of IL‐17 by innate and adaptive immune cells allows the presence of this important cytokine at distinct parts of the immune response. Notably, T lymphocytes can acquire the IL‐17 effector function in either the thymus or the periphery. Although CD4+IL17+ T lymphocytes are generally considered to be reciprocal in effector functions compared to Foxp3+ regulatory T cells, the presence of IL‐17+Foxp3+ cells requires additional characterisation. Notably, strong evidence also implicates IL‐17‐producing T lymphocytes in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus and asthma. It has been suggested that T lymphocytes such as IL17+Foxp3+ T lymphocytes, bearing aberrant effector functions, may be contributors to autoimmunity.

Key Concepts

  • Transcription factors are critical in the skewing of T lymphocyte effector functions.
  • Interleukin 17 (IL‐17) is a cytokine which is critical in the regulation of bacterial communities and fungi within mammalian host organisms; however, it is also associated with autoimmunity.
  • Interleukin 17 can be produced by several T cell populations including αβ CD4+ cells, αβ CD8+ and γδ T lymphocytes.
  • IL‐17‐producing T lymphocytes are a heterogeneous population that elicits a spectrum of effector functions.
  • The IL‐17 effector function can be acquired in the thymus or periphery.
  • Although evidence suggests that IL‐17 production can drive immune events associated with autoimmunity, it is possible IL‐17 production may serve as a biomarker for T lymphocytes possessing varied autoimmune disease‐promoting effector functions.
  • Regulation of T lymphocyte stability may have efficacy in the prevention of autoimmune disease.

Keywords: cytokine; plasticity; effector function; homeostasis; transcription factor; autoimmunity; interleukin 17; T lymphocyte

Figure 1. There is more to T17s than IL‐17: ‘Simplified’ schematic showing that multiple T lymphocyte subsets are known to produce IL‐17. T lymphocytes are generated in the thymus (left), developing a T cell receptor (TCR, either alpha beta (αβ) or gamma delta (γδ)) and expression of the glycoproteins CD4 or CD8. In addition to the generation of a TCR, a subset of gd and ab T cells can also acquire the IL‐17 effector function in the thymus (denoted by green colour). In the periphery, naïve T cells (blue, not committed to a set of effector functions) can also acquire the IL‐17 effector function in addition to regulatory (yellow), IFNγ (red) or combination of effector functions (denoted by variable colours).
Figure 2. IL‐17‐producing T lymphocytes hold the balance between immune homeostasis and autoimmunity. This figure depicts an IL‐17‐producing T cell at the base of a seesaw, balancing immune homeostasis on one side and autoimmunity on the other. Many different T lymphocyte subsets can make IL‐17, and various subsets can be identified by the cell surface expression of CCR4, IL‐23R, CCR6 and CD161 (denoted by blue squares). In addition to our classic IL‐17 (IL‐17a), different subsets of IL‐17‐producing cells produce an assortment of cytokines shown surrounding our IL‐17‐producing cell (black). The assortment of cytokines produced is dominated by which transcription factors (depicted inside the cell) are activated. The varied cytokines (effector functions) mediated by distinct subsets of IL‐17‐producing T lymphocytes serve drive a shift towards immune homeostasis or autoimmunity.
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Larkin, Joseph(Jan 2016) Interleukin 17‐Producing T Lymphocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024248]