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The Journal of Immunology, 2001, 167: 6338-6347.
Copyright © 2001 by The American Association of Immunologists

SF20/IL-25, a Novel Bone Marrow Stroma-Derived Growth Factor That Binds to Mouse Thymic Shared Antigen-1 and Supports Lymphoid Cell Proliferation

Edgardo E. Tulin1,*, Nobuhisa Onoda*, Yasuhiko Nakata*, Masatsugu Maeda*, Masakazu Hasegawa*, Hitoshi Nomura* and Toshio Kitamura{dagger}

* Chugai Research Institute for Molecular Medicine, Niihari, Ibaraki, Japan; and {dagger} Department of Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Using a forward genetic approach and phenotype-based complementation screening to search for factors that stimulate cell proliferation, we have isolated a novel secreted bone marrow stroma-derived growth factor, which we termed SF20/IL-25. This protein signals cells to proliferate via its receptor, which we have identified as mouse thymic shared Ag-1 (TSA-1). Enforced expression of TSA-1 in IL-3-dependent Ba/F3 cells that do not express endogenous TSA-1 rendered cells to proliferate in a dose-dependent manner when stimulated with SF20/IL-25. FDCP2, a factor-dependent hemopoietic cell line that expresses endogenous TSA-1, could also be stimulated to proliferate with SF20/IL-25. Binding of SF20 to TSA-1 was blocked by anti-TSA-1 Ab and SF20-induced proliferation of TSA-1-expressing cells was inhibited by anti-TSA-1. In vitro assay revealed that SF20/IL-25 has no detectable myelopoietic activity but supports proliferation of cells in the lymphoid lineage.




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