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-beta 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, gamma(c) 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

The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2) / R.Y. Lan, C. Selmi, M.E. Gershwin. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - 31:1(2008 Aug), pp. 7-12. [10.1016/j.jaut.2008.03.002]

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

C. Selmi
Secondo
;
2008

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-beta 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, gamma(c) 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
FoxP3 ; interleukin-2 ; interleukin-17 ; regulatory T cells ; autoimmunity
Settore MED/09 - Medicina Interna
ago-2008
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0896841108000267-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 403.26 kB
Formato Adobe PDF
403.26 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/63299
Citazioni
  • ???jsp.display-item.citation.pmc??? 48
  • Scopus 125
  • ???jsp.display-item.citation.isi??? 113
social impact