Interleukin-15 (11-15) is a cytokine present under different forms (secreted, membrane-bound, intracytoplasmic and nuclear) mediating different functions. Its receptor is composed of three chains (IL-15Rα/β /γc) displaying several different functional associations (IL-15Rα, IL-15Rα/β/γc, IL-15Rα/γc, IL-15Rα/γc). IL-15 is considered the most powerful physiological inducer of the differentiation of human hematopoietic progenitors (HP) into NK cells. It is likely that IL-15 could display a broader spectrum of regulatory functions on hematopoiesis more important than it has been previously suspected. Unprimed HP CD34+ cells constitutively secrete an endogenous, IL-15 (ES-IL-15) that controls, through autocrine/paracrine loops, several transcription factors and molecules playing a central role in the control of hematopoiesis. Nevertheless, ES-IL-15 is not competent for triggering HP differentiation into NK cells, likely due to the presence of a novel hybrid receptor composed of the γc and the GM-CSIFIRβ able to interfere on the signals of both IL-15 and GM-CSF. Finally, a novel type of membrane-bound IL-15 (IL-15mb) is expressed on human stromal spleen (derived myofibroblasts) and retained on the surface by the IL-15RIα/γc complex. Contact with this IL-15mb: 1) is necessary and sufficient for inducing the differentiation of circulating HP into cytolytic NK cells; 2) modifies the signalling pathways controlled by the ES-IL-15 in CB HP. Furthermore, IL-15mb signalling is heavily conditioned by the presence on surrounding cells of the IL-15Ra chain that activates some pathways (NFKB and STAT6), while inhibiting other (STAT3 et STAT5) that play a key role in the control of myelopoiesis. IL-15, through the cross-talk between its different forms and the different composition of IL-15R, could be one of the important regulatory factors of normal hematopoiesis. Alterations of these interactions could generate not only dysmyelopoiesis, but also survival and expansion of some leukemic clones.
|Translated title of the contribution||Interleukin-15 and hematopoiesis|
|Number of pages||11|
|Publication status||Published - Mar 2004|
- Signal transduction
ASJC Scopus subject areas