The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2)

Ruth Y. Lan, Carlos Selmi, M. Eric Gershwin

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Signaling through IL-2 induces the activation of pathways that lead to the proliferation, survival and cytokine production of effector T cells. However, through negative feedback mechanisms, internalization of the IL-2 receptor, induction of activation-induced cell death, and the generation of regulatory T cells, IL-2 also promotes the suppression of inflammatory responses. In regulatory T cells, IL-2 signaling upregulates the expression of FoxP3. Regulatory T cell induction by TGF-β also requires IL-2. Additionally, pro-inflammatory and pro-survival pathways involving PI3K upon IL-2 stimulation is inhibited by PTEN in regulatory T cells. Importantly, IL-2 signaling is key for the development, expansion and maintenance of regulatory T cells. However, γc cytokines can replace requirements for IL-2 in regulatory T cells, although not with the same efficacy. The dual roles of IL-2 in inflammation are demonstrated in that mice deficient in both FoxP3 and IL-2 display less severe symptoms compared to FoxP3 deficient mice. Finally, IL-2 not only plays a key role in the induction of effector T cells and regulatory T cells, it also inhibits IL-17 producing T cells. By understanding complex dynamics of IL-2 interactions in the inflammatory response, therapies may be developed or modified for regulating immune related diseases.

Original languageEnglish (US)
Pages (from-to)7-12
Number of pages6
JournalJournal of Autoimmunity
Volume31
Issue number1
DOIs
StatePublished - Aug 2008

Fingerprint

Regulatory T-Lymphocytes
Interleukin-2
T-Lymphocytes
Cytokines
Interleukin-17
Interleukin-2 Receptors
Immune System Diseases
Phosphatidylinositol 3-Kinases
Cell Death
Up-Regulation
Maintenance
Inflammation

Keywords

  • Autoimmunity
  • FoxP3
  • Interleukin-17
  • Interleukin-2
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2). / Lan, Ruth Y.; Selmi, Carlos; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 31, No. 1, 08.2008, p. 7-12.

Research output: Contribution to journalArticle

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