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Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites

Nature volume 392, pages 90–93 (1998)Cite this article

Abstract

The cytokine interleukin-3 (IL-3), which can be derived from T cells and other sources, is a potentially important link between the immune and haematopoietic systems1. IL-3 may be particularly critical for the development, survival and function of tissue mast cells1,2,3,4,5,6 and blood basophils7,8, which are thought to be important effector cells in immunity to parasites and other immunological responses, such as allergic reactions9. Here we show, using IL-3-deficient mice10, that IL-3 is not essential for the generation of mast cells or basophils under physiological conditions, but that it does contribute to increased numbers of tissue mast cells, enhanced basophil production, and immunity in mice infected with the nematode Stronglyoides venezuelensis. Parasite expulsion and mast-cell development are impaired even more severely in IL-3-deficient mice that also show a marked reduction in signalling by c-kit. These findings establish a role for IL-3 in immunity to parasites and indicate that one of the functions of IL-3 in host defence against infection is to expand populations of haematopoietic effector cells.

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Figure 1: Differential requirements for IL-3 in SCF-induced mast-cell development.
Figure 2: Defective parasite immunity and parasite-enhanced basophil and mast-cell development in IL-3−/− mice compared with.
Figure 3: Markedly defective responses to Stronglyoides venezuelensis infection areseen in KitW/KitW-v, IL-3−/− mice.

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References

  1. Ihle, J. N. Interleukin-3 and hematopoiesis. Chem. Immunol. 51, 65–106 (1992).

    CAS  PubMed  Google Scholar 

  2. Ihle, J. N. et al. Biological properties of homogeneous interleukin 3. I. Demonstration of WEHI-3 growth factor activity, mast cell growth factor activity, P cell stimulating factor activity and histamine producing factor activity. J. Immunol. 131, 282–287 (1983).

    CAS  PubMed  Google Scholar 

  3. Madden, K. B. et al. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J.Immunol. 147, 1387–1391 (1991).

    CAS  PubMed  Google Scholar 

  4. Finkelman, F. D. et al. Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine–anti-cytokine antibody complexes. J. Immunol. 151, 1235–1244 (1993).

    CAS  PubMed  Google Scholar 

  5. Svetic, A. et al. Aprimary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3. J. Immunol. 150, 3434–3441 (1993).

    CAS  PubMed  Google Scholar 

  6. Rodewald, H.-R., Dessing, M., Dvorak, A. M. & Galli, S. J. Identification of a committed precursor for the mast cell lineage. Science 271, 818–822 (1996).

    Article  ADS  CAS  Google Scholar 

  7. Saito, H. et al. Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins. Proc. Natl Acad. Sci. USA 85, 2288–2292 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Mayer, P., Valent, P., Schmidt, G., Liehl, E. & Bettelheim, P. The in vivo effects of recombinant human interleukin-3: demonstration of basophil differentiation factor, histamine-producing activity, and priming of GM-CSF-responsive progenitors in nonhuman primates. Blood 74, 613–621 (1989).

    CAS  PubMed  Google Scholar 

  9. Paul, W. E., Seder, R. A. & Plaut, M. Lymphokine and cytokine production by FcεRI+ cells. Adv. Immunol. 53, 1–29 (1993).

    Article  CAS  Google Scholar 

  10. Mach, N. et al. Involvement of interleukin-3 in delayed-type hypersensitivity. Blood (in the press)

  11. Ichihara, M. et al. Impaired interleukin-3 (IL-3) response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor α subunit gene. EMBO J. 14, 939–950 (1995).

    Article  CAS  Google Scholar 

  12. Nishinakamura, R., Miyajima, A., Mee, P. J., Tybulewicz, V. L. J. & Murray, R. Hematopoiesis in mice lacking the entire granulocyte–macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions. Blood 88, 2458–2464 (1996).

    CAS  PubMed  Google Scholar 

  13. Galli, S. J., Zsebo, K. M. & Geissler, E. N. The kit ligand, stem cell factor. Adv. Immunol. 55, 1–96 (1994).

    CAS  PubMed  Google Scholar 

  14. Tsuji, K., Zsebo, K. M. & Ogawa, M. Murine mast cell colony formation supported by IL-3, IL-4, and recombinant rat stem cell factor, ligand for c-kit. J. Cell. Physiol. 148, 362–369 (1991).

    Article  CAS  Google Scholar 

  15. Khalil, R. M. A. et al. Schistosoma mansoni infection in mice augments the capacity for interleukin 3 (IL-3) and IL-9 production and concurrently enlarges progenitor pools for mast cells and granulocytes–macrophages. Infect. Immun. 64, 4960–4966 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Nawa, Y. et al. Selective effector mechanisms for the expulsion of intestinal helminths. Parasite Immunol. 16, 333–338 (1994).

    Article  CAS  Google Scholar 

  17. Khan, A. I., Horii, Y., Tiuria, R., Sato, Y. & Nawa, Y. Mucosal mast cells and the expulsive mechanisms of mice against Stronglyoides venezuelensis. Int. J. Parasitol. 23, 551–555 (1993).

    Article  CAS  Google Scholar 

  18. Nocka, K. et al. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41, and W. EMBO J. 9, 1805–1813 (1990).

    Article  CAS  Google Scholar 

  19. Hayashi, S., Kunisada, T., Ogawa, M., Yamaguchi, K. & Nishikawa, S. Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse. Nucleic Acids Res. 19, 1267–1271 (1991).

    Article  CAS  Google Scholar 

  20. Kitamura, Y., Go, S. & Hatanaka, K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 52, 447–452 (1978).

    CAS  PubMed  Google Scholar 

  21. Jacoby, W., Cammarata, P. V., Findlay, S. & Pincus, S. H. Anaphylaxis in mast cell-deficient mice. J.Invest. Dermatol. 83, 302–304 (1984).

    Article  CAS  Google Scholar 

  22. Galli, S. J. & Kitamura, Y. Animal models of human disease. Genetically mast-cell-deficient W/Wv and Sl/Sld mice: their value for the analysis of the roles of mast cells in biological responses in vivo. Am. J. Pathol. 127, 191–198 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Ody, C., Kindler, V. & Vassalli, P. Interleukin 3 perfusion in W/Wv mice allows the development of macroscopic hematopoietic spleen colonies and restores cutaneous mast cell numbers. J. Exp. Med. 172, 403–406 (1990).

    Article  CAS  Google Scholar 

  24. Donaldson, L. E., Schmitt, E., Huntley, J. F., Newlands, G. F. J. & Grencis, R. K. Acritical role for stem cell factor and c-kit in host protective immunity to an intestinal helminth. Int. Immunol. 8, 559–567 (1996).

    Article  CAS  Google Scholar 

  25. Maeda, H. et al. Requirement of c-kit for development of intestinal pacemaker system. Development 116, 369–375 (1992).

    CAS  PubMed  Google Scholar 

  26. Puddington, L., Olson, S. & Lefrancois, L. Interactions between stem cell factor and c-kit are required for intestinal immune system homeostasis. Immunity 1, 733–739 (1994).

    Article  CAS  Google Scholar 

  27. Tsai, M. et al. Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor. Proc. Natl Acad. Sci. USA 88, 6382–6386 (1991).

    Article  ADS  CAS  Google Scholar 

  28. Tsai, M. et al. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype. J. Exp. Med. 174, 125–131 (1991).

    Article  CAS  Google Scholar 

  29. Sato, Y. & Toma, H. Effets of spleen cells and serum on transfer of immunity to Stronglyoides venezuelensis infection in hyothymic (nude) mice. Int. J. Parasitol. 20, 63–67 (1990).

    Article  CAS  Google Scholar 

  30. Lantz, C. S. et al. IgE regulates mouse basophil FcεRI expression in vivo. J. Immunol. 158, 2517–2521 (1997).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Z.-S. Wang, M. Yamaguchi, L. Fox and S. Fish for experimental assistance. This work was supported by USPHS grants (S.J.G.), the Claudia Adams Barr Foundation, a Young Markey Scientist Award and the Cancer Research Institute/Partridge Foundation (G.D.), the Roche Research Foundation (J.B.), the Korea Science and Engineering Foundation (C.H.S.) and the Swiss National Science Foundation (N.M.)

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Authors and Affiliations

  1. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, 02215, Massachusetts, USA

    Chris S. Lantz, Jurg Boesiger, Chang Ho Song & Stephen J. Galli

  2. Department of Medicine, Dana-Farber Cancer Institute and Harvard Medical School, Boston, 02115, Massachusetts, USA

    Nicolas Mach & Glenn Dranoff

  3. Department of Parasitology, Miyazaki Medical College, Kiyotake, 889-16, Miyazaki, Japan

    Takahiko Kobayashi & Yukifumi Nawa

  4. Department of Genetics, Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, 02115, Massachusetts, Boston, USA

    Richard C. Mulligan

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Lantz, C., Boesiger, J., Song, C. et al. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392, 90–93 (1998). https://doi.org/10.1038/32190

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