Interleukin 13 : novel role in direct regulation of proliferation and differentiation of primitive hematopoietic progenitor cells

• Published in: The Journal of experimental medicine Vol. 180; no. 1; pp. 75 - 82
• Main Authors: JACOBSEN, S. E. W, OKKENHAUG, C, VEIBY, O. P, CAPUT, D, FERRARA, P, MINTY, A
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.07.1994; The Rockefeller University Press
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Cell Differentiation - drug effects; Cell Division - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Cell Growth Factors - pharmacology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Immunobiology; Interleukin-11 - pharmacology; Interleukin-13; Interleukin-4 - pharmacology; Interleukins - pharmacology; Lymphokines, interleukins ( function, expression); Mice; Mice, Inbred C57BL; Recombinant Proteins - pharmacology; Regulatory factors and their cellular receptors; Stem Cell Factor; Cell proliferation; Vertebrata; Mammalia; Mouse; Hematopoiesis; Cytokine; Rodentia; Hematopoietic cell; Immune regulation; Cell differentiation; Precursor; Biological activity
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.180.1.75

The recently cloned interleukin 13 (IL-13) shares most investigated biological activities on B lymphocytes and monocytes with IL-4. In this study we investigated for the first time the potential role of IL-13 in the regulation of the growth of hematopoietic progenitor cells. IL-13 enhanced stem cell factor (SCF)-induced proliferation of Lin-Sca-1+ bone marrow progenitor cells more potently than IL-4. The effect of IL-13 was purely synergistic, since IL-13 alone stimulated no colony formation. Single cell experiments suggested that the synergistic effect of IL-13 on Lin-Sca-1+ progenitors was directly mediated. In contrast, IL-13 had no synergistic activity on SCF-induced proliferation of the more mature Lin-Sca-1- progenitor cells. Thus, the cloning frequency in response to SCF + IL-13 was at least 20-fold higher in the Lin-Sca-1+ than the Lin-Sca-1- progenitor cell population. Furthermore, IL-13 but not IL-4 synergistically enhanced colony formation of Lin-Sca-1+ progenitors in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) (threefold), whereas both IL-4 and IL-13 enhanced G-CSF-induced colony formation (threefold), and neither of the two significantly affected CSF-1 and IL-3-induced proliferation. Finally, whereas stimulation of Lin-Sca-1+ progenitors by SCF + G-CSF resulted in the formation of 90% granulocytes, the addition of IL-13 resulted in the production of macrophages exclusively. This novel effect on differentiation was directly mediated, shared with IL-4, and could not be observed on Lin-Sca-1- progenitor cells. Collectively, these findings indicate a novel role of IL-13 in early myelopoiesis, partially overlapping but also different from that of IL-4.