The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2).
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.
Lan
Ruth Y
RY
Division of Rheumatology, Allergy and Clinical Immunology, Genome and Biomedical Sciences Facility, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
Selmi
Carlos
C
Gershwin
M Eric
ME
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D025461:Feedback, Physiological / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2