IL15

Waldmann T., Tagaya Y.

IL-15 is a 14-15 к Da member of the four a helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular. IL-15 is post-translationally regulated by multiple controlling elements that impede translation, including 13 upstream AUGs of the 5′ UTR. two 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 type 1 IL-15 receptor includes IL-2/ 15R/i and 7c subunits which are shared with IL-2 as well as an IL-15-specific receptor subunit. IL-15Ro.. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2R but uses a novel 60-65 kDa IL-15RX subunit. This type 2 receptor signaling involves JAK2/STAT5 activation rather than the^JAKl/JAK3 and STAT5/STAT3 system used by the type 1 system 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, inflammatory bowel disease, and in diseases associated with the retroviruses HIV and HTLV-L New approaches inhibiting the action of IL-15. its receptor or its signaling pathway may be of value in the therapy of these diseases.