Combined stimulation with the T helper cell type 2 cytokines interleukin (IL)-4 and IL-10 induces mouse mast cell apoptosis

• Published in: The Journal of experimental medicine Vol. 192; no. 8; pp. 1093 - 1104
• Main Authors: Yeatman, 2nd, C F, Jacobs-Helber, S M, Mirmonsef, P, Gillespie, S R, Bouton, L A, Collins, H A, Sawyer, S T, Shelburne, C P, Ryan, J J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 16.10.2000
• Subjects: Animals; Annexin A5 - analysis; Apoptosis - drug effects; Apoptosis - immunology; Bone Marrow Cells - cytology; Cells, Cultured; Flow Cytometry; Interleukin-10 - pharmacology; Interleukin-3 - pharmacology; Interleukin-4 - pharmacology; Kinetics; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - physiology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Original; Recombinant Proteins - pharmacology; Stem Cell Factor - pharmacology; Th2 Cells - immunology
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.192.8.1093

Mast cells are found in connective and mucosal tissues throughout the body. Their activation via immunoglobulin E (IgE)-antigen interactions is promoted by T helper cell type 2 (Th2) cytokines and leads to the sequelae of allergic disease. We now report a mechanism by which Th2 cytokines can regulate mast cell survival. Specifically, we find that interleukin (IL)-4 and IL-10 induce apoptosis in IL-3-dependent bone marrow-derived mast cells and peritoneal mast cells. This process required 6 d of costimulation with IL-3, IL-4, and IL-10, and expression of signal transducer and activator of transcription 6 (Stat6). Apoptosis was coupled with decreased expression of bcl-x(L) and bcl-2. While this process occurred independent of the Fas pathway, culture in IL-3+IL-4+IL-10 greatly sensitized mast cells to Fas-mediated death. Additionally, we found that IgE cross-linkage or stimulation with stem cell factor enhanced the apoptotic abilities of IL-4 and IL-10. Finally, IL-3-independent mastocytomas and mast cell lines were resistant to apoptosis induced by IL-3+IL-4+IL-10. These data offer evidence of Th2 cytokine-mediated homeostasis whereby these cytokines both elicit and limit allergic responses. Dysregulation of this pathway may play a role in allergic disease and mast cell tumor survival.