The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens.

Annu Rev Immunol. 1999;17:19-49. Unique Identifier : AIDSLINE MED/99286804
Waldmann TA; Tagaya Y; Metabolism Branch, National Cancer Institute, National Institutes; of Health, Bethesda, Maryland, USA. tawald@helix.nih.gov

Abstract: Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15R beta and gamma c subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15R alpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.

Keywords: JOURNAL ARTICLE REVIEW REVIEW, ACADEMIC Animal Autoimmune Diseases/IMMUNOLOGY Base Sequence Cell Differentiation DNA, Complementary/GENETICS Gene Expression Regulation Human Immunosuppression Immunotherapy Inflammation/IMMUNOLOGY Interleukin-15/*GENETICS/*PHYSIOLOGY Killer Cells, Natural/CYTOLOGY/*IMMUNOLOGY Neoplasms/IMMUNOLOGY Receptors, Interleukin-2/PHYSIOLOGY Retroviridae Infections/IMMUNOLOGY Signal Transduction
991130
A99B1099

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